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Markus M. Heimesaat - One of the best experts on this subject based on the ideXlab platform.
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Immune-Modulatory Effects upon Oral Application of Cumin-Essential-Oil to Mice Suffering from Acute Campylobacteriosis
'MDPI AG', 2021Co-Authors: Soraya Mousavi, Stefan Bereswill, Dennis Weschka, Markus M. HeimesaatAbstract:Human Campylobacteriosis, commonly caused by Campylobacter jejuni, is a food-borne infection with rising prevalence causing significant health and socioeconomic burdens worldwide. Given the threat from emerging antimicrobial resistances, the treatment of infectious diseases with antibiotics-independent natural compounds is utmost appreciated. Since the health-beneficial effects of cumin-essential-oil (EO) have been known for centuries, its potential anti-pathogenic and immune-modulatory effects during acute experimental Campylobacteriosis were addressed in the present study. Therefore, C. jejuni-challenged secondary abiotic IL-10-/- mice were treated perorally with either cumin-EO or placebo starting on day 2 post-infection. On day 6 post-infection, cumin-EO treated mice harbored lower ileal pathogen numbers and exhibited a better clinical outcome when compared to placebo controls. Furthermore, cumin-EO treatment alleviated enteropathogen-induced apoptotic cell responses in colonic epithelia. Whereas, on day 6 post-infection, a dampened secretion of pro-inflammatory mediators, including nitric oxide and IFN-γ to basal levels, could be assessed in mesenteric lymph nodes of cumin-EO treated mice, systemic MCP-1 concentrations were elevated in placebo counterparts only. In conclusion, our preclinical intervention study provides first evidence for promising immune-modulatory effects of cumin-EO in the combat of human Campylobacteriosis. Future studies should address antimicrobial and immune-modulatory effects of natural compounds as adjunct antibiotics-independent treatment option for infectious diseases
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human Campylobacteriosis a serious infectious threat in a one health perspective
Current Topics in Microbiology and Immunology, 2021Co-Authors: Markus M. Heimesaat, Steffen Backert, Thomas Alter, Stefan BereswillAbstract:Zoonotic Campylobacter species-mainly C. jejuni and C. coli-are major causes of food-borne bacterial infectious gastroenteritis worldwide. Symptoms of intestinal Campylobacteriosis include abdominal pain, diarrhea and fever. The clinical course of enteritis is generally self-limiting, but some infected individuals develop severe post-infectious sequelae including autoimmune disorders affecting the nervous system, the joints and the intestinal tract. Moreover, in immunocompromised individuals, systemic spread of the pathogens may trigger diseases of the circulatory system and septicemia. The socioeconomic costs associated with Campylobacter infections have been calculated to several billion dollars annually. Poultry meat products represent major sources of human infections. Thus, a "One World-One Health" approach with collective efforts of public health authorities, veterinarians, clinicians, researchers and politicians is required to reduce the burden of Campylobacteriosis. Innovative intervention regimes for the prevention of Campylobacter contaminations along the food chain include improvements of information distribution to strengthen hygiene measures for agricultural remediation. Given that elimination of Campylobacter from the food production chains is not feasible, novel intervention strategies fortify both the reduction of pathogen contamination in food production and the treatment of the associated diseases in humans. This review summarizes some current trends in the combat of Campylobacter infections including the combination of public health and veterinary preventive approaches with consumer education. The "One World-One Health" perspective is completed by clinical aspects and molecular concepts of human Campylobacteriosis offering innovative treatment options supported by novel murine infection models that are based on the essential role of innate immune activation by bacterial endotoxins.
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novel clinical campylobacter jejuni infection models based on sensitization of mice to lipooligosaccharide a major bacterial factor triggering innate immune responses in human Campylobacteriosis
Microorganisms, 2020Co-Authors: Soraya Mousavi, Stefan Bereswill, Markus M. HeimesaatAbstract:: Human Campylobacter jejuni infections inducing Campylobacteriosis including post-infectious sequelae such as Guillain-Barre syndrome and reactive arthritis are rising worldwide and progress into a global burden of high socioeconomic impact. Intestinal immunopathology underlying Campylobacteriosis is a classical response of the innate immune system characterized by the accumulation of neutrophils and macrophages which cause tissue destruction, barrier defects and malabsorption leading to bloody diarrhea. Clinical studies revealed that enteritis and post-infectious morbidities of human C. jejuni infections are strongly dependent on the structure of pathogenic lipooligosaccharides (LOS) triggering the innate immune system via Toll-like-receptor (TLR)-4 signaling. Compared to humans, mice display an approximately 10,000 times weaker TLR-4 response and a pronounced colonization resistance (CR) against C. jejuni maintained by the murine gut microbiota. In consequence, investigations of Campylobacteriosis have been hampered by the lack of experimental animal models. We here summarize recent progress made in the development of murine C. jejuni infection models that are based on the abolishment of CR by modulating the murine gut microbiota and by sensitization of mice to LOS. These advances support the major role of LOS driven innate immunity in pathogenesis of Campylobacteriosis including post-infectious autoimmune diseases and promote the preclinical evaluation of novel pharmaceutical strategies for prophylaxis and treatment.
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carvacrol ameliorates acute Campylobacteriosis in a clinical murine infection model
Gut Pathogens, 2020Co-Authors: Soraya Mousavi, Anna-maria Schmidt, Ulrike Escher, Stefan Bereswill, Sophie Kittler, Corinna Kehrenberg, Elisa Thunhorst, Markus M. HeimesaatAbstract:The prevalence of human infections with the zoonotic pathogen Campylobacter jejuni is rising worldwide. Therefore, the identification of compounds with potent anti-pathogenic and anti-inflammatory properties for future therapeutic and/or preventive application to combat Campylobacteriosis is of importance for global health. Results of recent studies suggested carvacrol (4-isopropyl-2-methylphenol) as potential candidate molecule for the treatment of Campylobacteriosis in humans and for the prevention of Campylobacter colonization in farm animals. To address this in a clinical murine infection model of acute Campylobacteriosis, secondary abiotic IL-10−/− mice were subjected to synthetic carvacrol via the drinking water starting 4 days before peroral C. jejuni challenge. Whereas at day 6 post-infection placebo treated mice suffered from acute enterocolitis, mice from the carvacrol cohort not only harbored two log orders of magnitude lower pathogen loads in their intestines, but also displayed significantly reduced disease symptoms. Alleviated Campylobacteriosis following carvacrol application was accompanied by less distinct intestinal apoptosis and pro-inflammatory immune responses as well as by higher numbers of proliferating colonic epithelial cells. Remarkably, the inflammation-ameliorating effects of carvacrol treatment were not restricted to the intestinal tract, but could also be observed in extra-intestinal organs such as liver, kidneys and lungs and, strikingly, systemically as indicated by lower IFN-γ, TNF, MCP-1 and IL-6 serum concentrations in carvacrol versus placebo treated mice. Furthermore, carvacrol treatment was associated with less frequent translocation of viable C. jejuni originating from the intestines to extra-intestinal compartments. The lowered C. jejuni loads and alleviated symptoms observed in the here applied clinical murine model for human Campylobacteriosis highlight the application of carvacrol as a promising novel option for both, the treatment of Campylobacteriosis and hence, for prevention of post-infectious sequelae in humans, and for the reduction of C. jejuni colonization in the intestines of vertebrate lifestock animals.
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Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model
Gut Pathogens, 2019Co-Authors: Anna-maria Schmidt, Ulrike Escher, Soraya Mousavi, Nicole Tegtmeyer, Manja Boehm, Steffen Backert, Stefan Bereswill, Markus M. HeimesaatAbstract:Background Campylobacter jejuni infections constitute serious threats to human health with increasing prevalences worldwide. Our knowledge regarding the molecular mechanisms underlying host–pathogen interactions is still limited. Our group has established a clinical C. jejuni infection model based on abiotic IL-10^−/− mice mimicking key features of human Campylobacteriosis. In order to further validate this model for unraveling pathogen-host interactions mounting in acute disease, we here surveyed the immunopathological features of the important C. jejuni virulence factors FlaA and FlaB and the major adhesin CadF ( Campylobacter adhesin to fibronectin), which play a role in bacterial motility, protein secretion and adhesion, respectively. Methods and results Therefore, abiotic IL-10^−/− mice were perorally infected with C. jejuni strain 81-176 (WT) or with its isogenic flaA/B (Δ flaA/B ) or cadF (Δ cadF ) deletion mutants. Cultural analyses revealed that WT and Δ cadF but not Δ flaA/B bacteria stably colonized the stomach, duodenum and ileum, whereas all three strains were present in the colon at comparably high loads on day 6 post-infection. Remarkably, despite high colonic colonization densities, murine infection with the Δ flaA/B strain did not result in overt Campylobacteriosis, whereas mice infected with Δ cadF or WT were suffering from acute enterocolitis at day 6 post-infection. These symptoms coincided with pronounced pro-inflammatory immune responses, not only in the intestinal tract, but also in other organs such as the liver and kidneys and were accompanied with systemic inflammatory responses as indicated by increased serum MCP-1 concentrations following C. jejuni Δ cadF or WT, but not Δ flaA/B strain infection. Conclusion For the first time, our observations revealed that the C. jejuni flagellins A/B, but not adhesion mediated by CadF, are essential for inducing murine Campylobacteriosis. Furthermore, the secondary abiotic IL-10^−/− infection model has been proven suitable not only for detailed investigations of immunological aspects of Campylobacteriosis, but also for differential analyses of the roles of distinct C. jejuni virulence factors in induction and progression of disease.
Stefan Bereswill - One of the best experts on this subject based on the ideXlab platform.
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Immune-Modulatory Effects upon Oral Application of Cumin-Essential-Oil to Mice Suffering from Acute Campylobacteriosis
'MDPI AG', 2021Co-Authors: Soraya Mousavi, Stefan Bereswill, Dennis Weschka, Markus M. HeimesaatAbstract:Human Campylobacteriosis, commonly caused by Campylobacter jejuni, is a food-borne infection with rising prevalence causing significant health and socioeconomic burdens worldwide. Given the threat from emerging antimicrobial resistances, the treatment of infectious diseases with antibiotics-independent natural compounds is utmost appreciated. Since the health-beneficial effects of cumin-essential-oil (EO) have been known for centuries, its potential anti-pathogenic and immune-modulatory effects during acute experimental Campylobacteriosis were addressed in the present study. Therefore, C. jejuni-challenged secondary abiotic IL-10-/- mice were treated perorally with either cumin-EO or placebo starting on day 2 post-infection. On day 6 post-infection, cumin-EO treated mice harbored lower ileal pathogen numbers and exhibited a better clinical outcome when compared to placebo controls. Furthermore, cumin-EO treatment alleviated enteropathogen-induced apoptotic cell responses in colonic epithelia. Whereas, on day 6 post-infection, a dampened secretion of pro-inflammatory mediators, including nitric oxide and IFN-γ to basal levels, could be assessed in mesenteric lymph nodes of cumin-EO treated mice, systemic MCP-1 concentrations were elevated in placebo counterparts only. In conclusion, our preclinical intervention study provides first evidence for promising immune-modulatory effects of cumin-EO in the combat of human Campylobacteriosis. Future studies should address antimicrobial and immune-modulatory effects of natural compounds as adjunct antibiotics-independent treatment option for infectious diseases
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human Campylobacteriosis a serious infectious threat in a one health perspective
Current Topics in Microbiology and Immunology, 2021Co-Authors: Markus M. Heimesaat, Steffen Backert, Thomas Alter, Stefan BereswillAbstract:Zoonotic Campylobacter species-mainly C. jejuni and C. coli-are major causes of food-borne bacterial infectious gastroenteritis worldwide. Symptoms of intestinal Campylobacteriosis include abdominal pain, diarrhea and fever. The clinical course of enteritis is generally self-limiting, but some infected individuals develop severe post-infectious sequelae including autoimmune disorders affecting the nervous system, the joints and the intestinal tract. Moreover, in immunocompromised individuals, systemic spread of the pathogens may trigger diseases of the circulatory system and septicemia. The socioeconomic costs associated with Campylobacter infections have been calculated to several billion dollars annually. Poultry meat products represent major sources of human infections. Thus, a "One World-One Health" approach with collective efforts of public health authorities, veterinarians, clinicians, researchers and politicians is required to reduce the burden of Campylobacteriosis. Innovative intervention regimes for the prevention of Campylobacter contaminations along the food chain include improvements of information distribution to strengthen hygiene measures for agricultural remediation. Given that elimination of Campylobacter from the food production chains is not feasible, novel intervention strategies fortify both the reduction of pathogen contamination in food production and the treatment of the associated diseases in humans. This review summarizes some current trends in the combat of Campylobacter infections including the combination of public health and veterinary preventive approaches with consumer education. The "One World-One Health" perspective is completed by clinical aspects and molecular concepts of human Campylobacteriosis offering innovative treatment options supported by novel murine infection models that are based on the essential role of innate immune activation by bacterial endotoxins.
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novel clinical campylobacter jejuni infection models based on sensitization of mice to lipooligosaccharide a major bacterial factor triggering innate immune responses in human Campylobacteriosis
Microorganisms, 2020Co-Authors: Soraya Mousavi, Stefan Bereswill, Markus M. HeimesaatAbstract:: Human Campylobacter jejuni infections inducing Campylobacteriosis including post-infectious sequelae such as Guillain-Barre syndrome and reactive arthritis are rising worldwide and progress into a global burden of high socioeconomic impact. Intestinal immunopathology underlying Campylobacteriosis is a classical response of the innate immune system characterized by the accumulation of neutrophils and macrophages which cause tissue destruction, barrier defects and malabsorption leading to bloody diarrhea. Clinical studies revealed that enteritis and post-infectious morbidities of human C. jejuni infections are strongly dependent on the structure of pathogenic lipooligosaccharides (LOS) triggering the innate immune system via Toll-like-receptor (TLR)-4 signaling. Compared to humans, mice display an approximately 10,000 times weaker TLR-4 response and a pronounced colonization resistance (CR) against C. jejuni maintained by the murine gut microbiota. In consequence, investigations of Campylobacteriosis have been hampered by the lack of experimental animal models. We here summarize recent progress made in the development of murine C. jejuni infection models that are based on the abolishment of CR by modulating the murine gut microbiota and by sensitization of mice to LOS. These advances support the major role of LOS driven innate immunity in pathogenesis of Campylobacteriosis including post-infectious autoimmune diseases and promote the preclinical evaluation of novel pharmaceutical strategies for prophylaxis and treatment.
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carvacrol ameliorates acute Campylobacteriosis in a clinical murine infection model
Gut Pathogens, 2020Co-Authors: Soraya Mousavi, Anna-maria Schmidt, Ulrike Escher, Stefan Bereswill, Sophie Kittler, Corinna Kehrenberg, Elisa Thunhorst, Markus M. HeimesaatAbstract:The prevalence of human infections with the zoonotic pathogen Campylobacter jejuni is rising worldwide. Therefore, the identification of compounds with potent anti-pathogenic and anti-inflammatory properties for future therapeutic and/or preventive application to combat Campylobacteriosis is of importance for global health. Results of recent studies suggested carvacrol (4-isopropyl-2-methylphenol) as potential candidate molecule for the treatment of Campylobacteriosis in humans and for the prevention of Campylobacter colonization in farm animals. To address this in a clinical murine infection model of acute Campylobacteriosis, secondary abiotic IL-10−/− mice were subjected to synthetic carvacrol via the drinking water starting 4 days before peroral C. jejuni challenge. Whereas at day 6 post-infection placebo treated mice suffered from acute enterocolitis, mice from the carvacrol cohort not only harbored two log orders of magnitude lower pathogen loads in their intestines, but also displayed significantly reduced disease symptoms. Alleviated Campylobacteriosis following carvacrol application was accompanied by less distinct intestinal apoptosis and pro-inflammatory immune responses as well as by higher numbers of proliferating colonic epithelial cells. Remarkably, the inflammation-ameliorating effects of carvacrol treatment were not restricted to the intestinal tract, but could also be observed in extra-intestinal organs such as liver, kidneys and lungs and, strikingly, systemically as indicated by lower IFN-γ, TNF, MCP-1 and IL-6 serum concentrations in carvacrol versus placebo treated mice. Furthermore, carvacrol treatment was associated with less frequent translocation of viable C. jejuni originating from the intestines to extra-intestinal compartments. The lowered C. jejuni loads and alleviated symptoms observed in the here applied clinical murine model for human Campylobacteriosis highlight the application of carvacrol as a promising novel option for both, the treatment of Campylobacteriosis and hence, for prevention of post-infectious sequelae in humans, and for the reduction of C. jejuni colonization in the intestines of vertebrate lifestock animals.
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Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model
Gut Pathogens, 2019Co-Authors: Anna-maria Schmidt, Ulrike Escher, Soraya Mousavi, Nicole Tegtmeyer, Manja Boehm, Steffen Backert, Stefan Bereswill, Markus M. HeimesaatAbstract:Background Campylobacter jejuni infections constitute serious threats to human health with increasing prevalences worldwide. Our knowledge regarding the molecular mechanisms underlying host–pathogen interactions is still limited. Our group has established a clinical C. jejuni infection model based on abiotic IL-10^−/− mice mimicking key features of human Campylobacteriosis. In order to further validate this model for unraveling pathogen-host interactions mounting in acute disease, we here surveyed the immunopathological features of the important C. jejuni virulence factors FlaA and FlaB and the major adhesin CadF ( Campylobacter adhesin to fibronectin), which play a role in bacterial motility, protein secretion and adhesion, respectively. Methods and results Therefore, abiotic IL-10^−/− mice were perorally infected with C. jejuni strain 81-176 (WT) or with its isogenic flaA/B (Δ flaA/B ) or cadF (Δ cadF ) deletion mutants. Cultural analyses revealed that WT and Δ cadF but not Δ flaA/B bacteria stably colonized the stomach, duodenum and ileum, whereas all three strains were present in the colon at comparably high loads on day 6 post-infection. Remarkably, despite high colonic colonization densities, murine infection with the Δ flaA/B strain did not result in overt Campylobacteriosis, whereas mice infected with Δ cadF or WT were suffering from acute enterocolitis at day 6 post-infection. These symptoms coincided with pronounced pro-inflammatory immune responses, not only in the intestinal tract, but also in other organs such as the liver and kidneys and were accompanied with systemic inflammatory responses as indicated by increased serum MCP-1 concentrations following C. jejuni Δ cadF or WT, but not Δ flaA/B strain infection. Conclusion For the first time, our observations revealed that the C. jejuni flagellins A/B, but not adhesion mediated by CadF, are essential for inducing murine Campylobacteriosis. Furthermore, the secondary abiotic IL-10^−/− infection model has been proven suitable not only for detailed investigations of immunological aspects of Campylobacteriosis, but also for differential analyses of the roles of distinct C. jejuni virulence factors in induction and progression of disease.
Soraya Mousavi - One of the best experts on this subject based on the ideXlab platform.
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Immune-Modulatory Effects upon Oral Application of Cumin-Essential-Oil to Mice Suffering from Acute Campylobacteriosis
'MDPI AG', 2021Co-Authors: Soraya Mousavi, Stefan Bereswill, Dennis Weschka, Markus M. HeimesaatAbstract:Human Campylobacteriosis, commonly caused by Campylobacter jejuni, is a food-borne infection with rising prevalence causing significant health and socioeconomic burdens worldwide. Given the threat from emerging antimicrobial resistances, the treatment of infectious diseases with antibiotics-independent natural compounds is utmost appreciated. Since the health-beneficial effects of cumin-essential-oil (EO) have been known for centuries, its potential anti-pathogenic and immune-modulatory effects during acute experimental Campylobacteriosis were addressed in the present study. Therefore, C. jejuni-challenged secondary abiotic IL-10-/- mice were treated perorally with either cumin-EO or placebo starting on day 2 post-infection. On day 6 post-infection, cumin-EO treated mice harbored lower ileal pathogen numbers and exhibited a better clinical outcome when compared to placebo controls. Furthermore, cumin-EO treatment alleviated enteropathogen-induced apoptotic cell responses in colonic epithelia. Whereas, on day 6 post-infection, a dampened secretion of pro-inflammatory mediators, including nitric oxide and IFN-γ to basal levels, could be assessed in mesenteric lymph nodes of cumin-EO treated mice, systemic MCP-1 concentrations were elevated in placebo counterparts only. In conclusion, our preclinical intervention study provides first evidence for promising immune-modulatory effects of cumin-EO in the combat of human Campylobacteriosis. Future studies should address antimicrobial and immune-modulatory effects of natural compounds as adjunct antibiotics-independent treatment option for infectious diseases
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novel clinical campylobacter jejuni infection models based on sensitization of mice to lipooligosaccharide a major bacterial factor triggering innate immune responses in human Campylobacteriosis
Microorganisms, 2020Co-Authors: Soraya Mousavi, Stefan Bereswill, Markus M. HeimesaatAbstract:: Human Campylobacter jejuni infections inducing Campylobacteriosis including post-infectious sequelae such as Guillain-Barre syndrome and reactive arthritis are rising worldwide and progress into a global burden of high socioeconomic impact. Intestinal immunopathology underlying Campylobacteriosis is a classical response of the innate immune system characterized by the accumulation of neutrophils and macrophages which cause tissue destruction, barrier defects and malabsorption leading to bloody diarrhea. Clinical studies revealed that enteritis and post-infectious morbidities of human C. jejuni infections are strongly dependent on the structure of pathogenic lipooligosaccharides (LOS) triggering the innate immune system via Toll-like-receptor (TLR)-4 signaling. Compared to humans, mice display an approximately 10,000 times weaker TLR-4 response and a pronounced colonization resistance (CR) against C. jejuni maintained by the murine gut microbiota. In consequence, investigations of Campylobacteriosis have been hampered by the lack of experimental animal models. We here summarize recent progress made in the development of murine C. jejuni infection models that are based on the abolishment of CR by modulating the murine gut microbiota and by sensitization of mice to LOS. These advances support the major role of LOS driven innate immunity in pathogenesis of Campylobacteriosis including post-infectious autoimmune diseases and promote the preclinical evaluation of novel pharmaceutical strategies for prophylaxis and treatment.
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carvacrol ameliorates acute Campylobacteriosis in a clinical murine infection model
Gut Pathogens, 2020Co-Authors: Soraya Mousavi, Anna-maria Schmidt, Ulrike Escher, Stefan Bereswill, Sophie Kittler, Corinna Kehrenberg, Elisa Thunhorst, Markus M. HeimesaatAbstract:The prevalence of human infections with the zoonotic pathogen Campylobacter jejuni is rising worldwide. Therefore, the identification of compounds with potent anti-pathogenic and anti-inflammatory properties for future therapeutic and/or preventive application to combat Campylobacteriosis is of importance for global health. Results of recent studies suggested carvacrol (4-isopropyl-2-methylphenol) as potential candidate molecule for the treatment of Campylobacteriosis in humans and for the prevention of Campylobacter colonization in farm animals. To address this in a clinical murine infection model of acute Campylobacteriosis, secondary abiotic IL-10−/− mice were subjected to synthetic carvacrol via the drinking water starting 4 days before peroral C. jejuni challenge. Whereas at day 6 post-infection placebo treated mice suffered from acute enterocolitis, mice from the carvacrol cohort not only harbored two log orders of magnitude lower pathogen loads in their intestines, but also displayed significantly reduced disease symptoms. Alleviated Campylobacteriosis following carvacrol application was accompanied by less distinct intestinal apoptosis and pro-inflammatory immune responses as well as by higher numbers of proliferating colonic epithelial cells. Remarkably, the inflammation-ameliorating effects of carvacrol treatment were not restricted to the intestinal tract, but could also be observed in extra-intestinal organs such as liver, kidneys and lungs and, strikingly, systemically as indicated by lower IFN-γ, TNF, MCP-1 and IL-6 serum concentrations in carvacrol versus placebo treated mice. Furthermore, carvacrol treatment was associated with less frequent translocation of viable C. jejuni originating from the intestines to extra-intestinal compartments. The lowered C. jejuni loads and alleviated symptoms observed in the here applied clinical murine model for human Campylobacteriosis highlight the application of carvacrol as a promising novel option for both, the treatment of Campylobacteriosis and hence, for prevention of post-infectious sequelae in humans, and for the reduction of C. jejuni colonization in the intestines of vertebrate lifestock animals.
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Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model
Gut Pathogens, 2019Co-Authors: Anna-maria Schmidt, Ulrike Escher, Soraya Mousavi, Nicole Tegtmeyer, Manja Boehm, Steffen Backert, Stefan Bereswill, Markus M. HeimesaatAbstract:Background Campylobacter jejuni infections constitute serious threats to human health with increasing prevalences worldwide. Our knowledge regarding the molecular mechanisms underlying host–pathogen interactions is still limited. Our group has established a clinical C. jejuni infection model based on abiotic IL-10^−/− mice mimicking key features of human Campylobacteriosis. In order to further validate this model for unraveling pathogen-host interactions mounting in acute disease, we here surveyed the immunopathological features of the important C. jejuni virulence factors FlaA and FlaB and the major adhesin CadF ( Campylobacter adhesin to fibronectin), which play a role in bacterial motility, protein secretion and adhesion, respectively. Methods and results Therefore, abiotic IL-10^−/− mice were perorally infected with C. jejuni strain 81-176 (WT) or with its isogenic flaA/B (Δ flaA/B ) or cadF (Δ cadF ) deletion mutants. Cultural analyses revealed that WT and Δ cadF but not Δ flaA/B bacteria stably colonized the stomach, duodenum and ileum, whereas all three strains were present in the colon at comparably high loads on day 6 post-infection. Remarkably, despite high colonic colonization densities, murine infection with the Δ flaA/B strain did not result in overt Campylobacteriosis, whereas mice infected with Δ cadF or WT were suffering from acute enterocolitis at day 6 post-infection. These symptoms coincided with pronounced pro-inflammatory immune responses, not only in the intestinal tract, but also in other organs such as the liver and kidneys and were accompanied with systemic inflammatory responses as indicated by increased serum MCP-1 concentrations following C. jejuni Δ cadF or WT, but not Δ flaA/B strain infection. Conclusion For the first time, our observations revealed that the C. jejuni flagellins A/B, but not adhesion mediated by CadF, are essential for inducing murine Campylobacteriosis. Furthermore, the secondary abiotic IL-10^−/− infection model has been proven suitable not only for detailed investigations of immunological aspects of Campylobacteriosis, but also for differential analyses of the roles of distinct C. jejuni virulence factors in induction and progression of disease.
Tanya Libby - One of the best experts on this subject based on the ideXlab platform.
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association between community socioeconomic factors animal feeding operations and Campylobacteriosis incidence rates foodborne diseases active surveillance network foodnet 2004 2010
BMC Infectious Diseases, 2016Co-Authors: Rachel Rosenberg E Goldstein, Raul Cruzcano, David Blythe, Patricia Ryan, Chengsheng Jiang, Amanda C Palmer, Brenna Hogan, Benjamin White, John R Dunn, Tanya LibbyAbstract:Background Campylobacter is a leading cause of foodborne illness in the United States. Campylobacter infections have been associated with individual risk factors, such as the consumption of poultry and raw milk. Recently, a Maryland-based study identified community socioeconomic and environmental factors that are also associated with Campylobacteriosis rates. However, no previous studies have evaluated the association between community risk factors and Campylobacteriosis rates across multiple U.S. states.
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association between community socioeconomic factors animal feeding operations and Campylobacteriosis incidence rates foodborne diseases active surveillance network foodnet 2004 2010
BMC Infectious Diseases, 2016Co-Authors: Rachel Rosenberg E Goldstein, Raul Cruzcano, David Blythe, Patricia Ryan, Chengsheng Jiang, Brenna Hogan, Benjamin White, John R Dunn, Amanda Palmer, Tanya LibbyAbstract:Campylobacter is a leading cause of foodborne illness in the United States. Campylobacter infections have been associated with individual risk factors, such as the consumption of poultry and raw milk. Recently, a Maryland-based study identified community socioeconomic and environmental factors that are also associated with Campylobacteriosis rates. However, no previous studies have evaluated the association between community risk factors and Campylobacteriosis rates across multiple U.S. states. We obtained Campylobacter case data (2004–2010; n = 40,768) from the Foodborne Diseases Active Surveillance Network (FoodNet) and socioeconomic and environmental data from the 2010 Census of Population and Housing, the 2011 American Community Survey, and the 2007 U.S. Census of Agriculture. We linked data by zip code and derived incidence rate ratios using negative binomial regression models. Community socioeconomic and environmental factors were associated with both lower and higher Campylobacteriosis rates. Zip codes with higher percentages of African Americans had lower rates of Campylobacteriosis (incidence rate ratio [IRR]) = 0.972; 95 % confidence interval (CI) = 0.970,0.974). In Georgia, Maryland, and Tennessee, three leading broiler chicken producing states, zip codes with broiler operations had incidence rates that were 22 % (IRR = 1.22; 95 % CI = 1.03,1.43), 16 % (IRR = 1.16; 95 % CI = 0.99,1.37), and 35 % (IRR = 1.35; 95 % CI = 1.18,1.53) higher, respectively, than those of zip codes without broiler operations. In Minnesota and New York FoodNet counties, two top dairy producing areas, zip codes with dairy operations had significantly higher Campylobacteriosis incidence rates (IRR = 1.37; 95 % CI = 1.22, 1.55; IRR = 1.19; 95 % CI = 1.04,1.36). Community socioeconomic and environmental factors are important to consider when evaluating the relationship between possible risk factors and Campylobacter infection.
N P French - One of the best experts on this subject based on the ideXlab platform.
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shifts in the molecular epidemiology of campylobacter jejuni infections in a sentinel region of new zealand following implementation of food safety interventions by the poultry industry
Applied and Environmental Microbiology, 2019Co-Authors: Antoine Nohra, Jonathan C Marshall, A Grinberg, Anne C Midwinter, J M Collinsemerson, N P FrenchAbstract:ABSTRACT In 2006, New Zealand had the highest notification rate of Campylobacteriosis in the world, and poultry was considered the leading source of Campylobacteriosis. Implementation of food safety interventions by the poultry industry led to a decrease in the Campylobacteriosis notification rate. The aim is to examine the impact of targeted food safety interventions implemented by the New Zealand poultry industry on the source attribution of Campylobacter jejuni infections in a sentinel region. Campylobacter jejuni isolates collected from the Manawatu region of New Zealand between 2005 and 2007 (“before intervention”) and 2008 and 2015 (“after intervention”) from human clinical cases, chicken meat, ruminant feces, environmental water, and wild bird sources were subtyped by multilocus sequence typing. Viable counts of Campylobacter spp. from carcasses were analyzed using a zero-inflated Poisson regression model. In the period before intervention, sequence type 474 (ST-474) was the most common sequence type (ST) recovered from human cases, accounting for 28.2% of the isolates. After intervention, the proportion of human cases positive for ST-474 reduced to 9.3%. Modeling indicated that chicken meat, primarily from one supplier, was the main source of C. jejuni infection in the Manawatu region before intervention. However, after intervention poultry collectively had a similar attribution to ruminants, but more human cases were attributed to ruminants than any single chicken supplier. Viable counts on carcasses were lower in all poultry suppliers after intervention. This study provides evidence of changes in the source attribution of Campylobacteriosis following targeted food safety interventions in one sector of the food supply chain. IMPORTANCE This study provides a unique insight into the effects of food safety interventions implemented in one sector of the food industry on the transmission routes of a major foodborne agent. Following the implementation of food safety interventions by the poultry industry, shifts in the molecular epidemiology of Campylobacter jejuni infections in a sentinel region of New Zealand were observed. Targeted interventions to reduce disease incidence are effective but require continued surveillance and analysis to indicate where further interventions may be beneficial.
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Campylobacteriosis in returning travellers and potential secondary transmission of exotic strains
Epidemiology and Infection, 2014Co-Authors: Lapo Mughinigras, Jaap A. Wagenaar, Ingrid H M Friesema, A H Havelaar, N P French, J H Smid, A G De Boer, Caterina Graziani, Luca Busani, W Van PeltAbstract:Multilocus sequence types (STs) were determined for 232 and 737 Campylobacter jejuni/coli isolates from Dutch travellers and domestically acquired cases, respectively. Putative risk factors for travel-related Campylobacteriosis, and for domestically acquired Campylobacteriosis caused by exotic STs (putatively carried by returning travellers), were investigated. Travelling to Asia, Africa, Latin America and the Caribbean, and Southern Europe significantly increased the risk of acquiring Campylobacteriosis compared to travelling within Western Europe. Besides eating chicken, using antacids, and having chronic enteropathies, we identified eating vegetable salad outside Europe, drinking bottled water in high-risk destinations, and handling/eating undercooked pork as possible risk factors for travel-related Campylobacteriosis. Factors associated with domestically acquired Campylobacteriosis caused by exotic STs involved predominantly person-to-person contacts around popular holiday periods. We concluded that putative determinants of travel-related Campylobacteriosis differ from those of domestically acquired infections and that returning travellers may carry several exotic strains that might subsequently spread to domestic populations even through limited person-to-person transmission.
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application of molecular epidemiology to understanding Campylobacteriosis in the canterbury region of new zealand
Epidemiology and Infection, 2013Co-Authors: B J Gilpin, Jonathan C Marshall, G Walshe, D Smith, N P FrenchAbstract:Pulsed-field gel electrophoresis genotypes of Campylobacter isolates from 603 human patients were compared with 485 isolates from retail offal (primarily chicken and lamb) to identify temporal clusters and possible sources of Campylobacteriosis. Detailed epidemiological information was collected from 364 of the patients, and when combined with genotyping data allowed a putative transmission pathway of Campylobacteriosis to be assigned for 88% of patients. The sources of infection were 47% food, 28% direct animal contact, 7% overseas travel, 4% person-to-person transmission and 3% water-related. A significant summer increase in Campylobacteriosis cases was primarily attributed to an increase in food-related cases. Genotyping of isolates was essential for identifying the likely cause of infection for individuals. However, a more rapid and cheaper typing tool for Campylobacter is needed, which if applied to human and animal isolates on a routine basis could advance greatly our understanding of the ongoing problem of Campylobacter infection in New Zealand.
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the spatial and temporal determinants of Campylobacteriosis notifications in new zealand 2001 2007
Epidemiology and Infection, 2012Co-Authors: Simon E F Spencer, Donald Campbell, Michael G Baker, Jonathan C Marshall, R Pirie, N P FrenchAbstract:Despite recent improvements, New Zealand still has one of the highest per-capita incidence rates of Campylobacteriosis in the world. To reduce the incidence, a thorough understanding of the epidemiology of infection is needed. This retrospective analysis of 36 000 notified human cases during a high-risk period between 2001 and 2007 explored the spatial and temporal determinants of Campylobacter notifications at a fine spatial scale in order to improve understanding of the complex epidemiology. Social deprivation was associated with a decreased risk of notification, whereas urban residence was associated with an increased risk. However, for young children rural residence was a risk factor. High dairy cattle density was associated with an increased risk of notification in two of the three regions investigated. Campylobacter notification patterns exhibit large temporal variations; however, few factors were associated with periods of increased risk, in particular temperature did not appear to drive the seasonality in Campylobacteriosis.
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risk factors for Campylobacteriosis of chicken ruminant and environmental origin a combined case control and source attribution analysis
PLOS ONE, 2012Co-Authors: Jaap A. Wagenaar, Ingrid H M Friesema, Lapo Mughini Gras, A H Havelaar, J H Smid, Albert G De Boer, N P FrenchAbstract:Background Campylobacteriosis contributes strongly to the disease burden of food-borne pathogens. Case-control studies are limited in attributing human infections to the different reservoirs because they can only trace back to the points of exposure, which may not point to the original reservoirs because of cross-contamination. Human Campylobacter infections can be attributed to specific reservoirs by estimating the extent of subtype sharing between strains from humans and reservoirs using multilocus sequence typing (MLST). Methodology/Principal Findings We investigated risk factors for human Campylobacteriosis caused by Campylobacter strains attributed to different reservoirs. Sequence types (STs) were determined for 696 C. jejuni and 41 C. coli strains from endemic human cases included in a case-control study. The asymmetric island model, a population genetics approach for modeling Campylobacter evolution and transmission, attributed these cases to four putative animal reservoirs (chicken, cattle, sheep, pig) and to the environment (water, sand, wild birds) considered as a proxy for other unidentified reservoirs. Most cases were attributed to chicken (66%) and cattle (21%), identified as the main reservoirs in The Netherlands. Consuming chicken was a risk factor for Campylobacteriosis caused by chicken-associated STs, whereas consuming beef and pork were protective. Risk factors for Campylobacteriosis caused by ruminant-associated STs were contact with animals, barbecuing in non-urban areas, consumption of tripe, and never/seldom chicken consumption. Consuming game and swimming in a domestic swimming pool during springtime were risk factors for Campylobacteriosis caused by environment-associated STs. Infections with chicken- and ruminant-associated STs were only partially explained by food-borne transmission; direct contact and environmental pathways were also important. Conclusion/Significance This is the first case-control study in which risk factors for Campylobacteriosis are investigated in relation to the attributed reservoirs based on MLST profiles. Combining epidemiological and source attribution data improved Campylobacteriosis risk factor identification and characterization, generated hypotheses, and showed that genotype-based source attribution is epidemiologically sensible.