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Ruth M Ruprecht - One of the best experts on this subject based on the ideXlab platform.
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schistosoma mansoni enhances Host Susceptibility to mucosal but not intravenous challenge by r5 clade c shiv
PLOS Neglected Tropical Diseases, 2011Co-Authors: Nagadenahalli B Siddappa, Girish Hemashettar, Vivekanandan Shanmuganathan, Amma A Semenya, Elizabeth Sweeney, Katherine Paul, Evan W Secor, Ruth M RuprechtAbstract:Background The high prevalence of HIV-1/AIDS in areas endemic for schistosomiasis and other helminthic infections has led to the hypothesis that parasites increase Host Susceptibility to immunodeficiency virus infection. We previously showed that rhesus macaques (RM) with active schistosomiasis were significantly more likely to become systemically infected after intrarectal (i.r.) exposure to an R5-tropic clade C simian-human immunodeficiency virus (SHIV-C) than were parasite-free controls. However, we could not address whether this was due to systemic or mucosal effects. If systemic immunoactivation resulted in increased Susceptibility to SHIV-C acquisition, a similarly large difference in Host Susceptibility would be seen after intravenous (i.v.) SHIV-C challenge. Conversely, if increased Host Susceptibility was due to parasite-induced immunoactivation at the mucosal level, i.v. SHIV-C challenge would not result in significant differences between parasitized and parasite-free monkeys. Methods and Findings We enrolled two groups of RM and infected one group with Schistosoma mansoni; the other group was left parasite-free. Both groups were challenged i.v. with decreasing doses of SHIV-C. No statistically significant differences in 50% animal infectious doses (AID50) or peak viremia were seen between the two groups. These data strongly contrast the earlier i.r. SHIV-C challenge (using the same virus stock) in the presence/absence of parasites, where we noted a 17-fold difference in AID50 and one log higher peak viremia in parasitized monkeys (P<0.001 for both). The lack of significant differences after the i.v. challenge implies that the increased Host Susceptibility is predominantly due to parasite-mediated mucosal upregulation of virus replication and spread, rather than systemic effects. Conclusions The major impact of schistosome-induced increased Host Susceptibility is at the mucosal level. Given that >90% of all new HIV-1 infections worldwide are acquired through mucosal contact, parasitic infections that inflame mucosae may play an important role in the spread of HIV-1.
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Schistosoma mansoni Enhances Host Susceptibility to Mucosal but Not Intravenous Challenge by R5 Clade C SHIV
PLOS Neglected Tropical Diseases, 2011Co-Authors: Nagadenahalli B Siddappa, Girish Hemashettar, Vivekanandan Shanmuganathan, Amma A Semenya, Elizabeth Sweeney, Katherine Paul, W. Evan Secor, Ruth M RuprechtAbstract:Background The high prevalence of HIV-1/AIDS in areas endemic for schistosomiasis and other helminthic infections has led to the hypothesis that parasites increase Host Susceptibility to immunodeficiency virus infection. We previously showed that rhesus macaques (RM) with active schistosomiasis were significantly more likely to become systemically infected after intrarectal (i.r.) exposure to an R5-tropic clade C simian-human immunodeficiency virus (SHIV-C) than were parasite-free controls. However, we could not address whether this was due to systemic or mucosal effects. If systemic immunoactivation resulted in increased Susceptibility to SHIV-C acquisition, a similarly large difference in Host Susceptibility would be seen after intravenous (i.v.) SHIV-C challenge. Conversely, if increased Host Susceptibility was due to parasite-induced immunoactivation at the mucosal level, i.v. SHIV-C challenge would not result in significant differences between parasitized and parasite-free monkeys. Methods and Findings We enrolled two groups of RM and infected one group with Schistosoma mansoni; the other group was left parasite-free. Both groups were challenged i.v. with decreasing doses of SHIV-C. No statistically significant differences in 50% animal infectious doses (AID50) or peak viremia were seen between the two groups. These data strongly contrast the earlier i.r. SHIV-C challenge (using the same virus stock) in the presence/absence of parasites, where we noted a 17-fold difference in AID50 and one log higher peak viremia in parasitized monkeys (P90% of all new HIV-1 infections worldwide are acquired through mucosal contact, parasitic infections that inflame mucosae may play an important role in the spread of HIV-1.
Nagadenahalli B Siddappa - One of the best experts on this subject based on the ideXlab platform.
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schistosoma mansoni enhances Host Susceptibility to mucosal but not intravenous challenge by r5 clade c shiv
PLOS Neglected Tropical Diseases, 2011Co-Authors: Nagadenahalli B Siddappa, Girish Hemashettar, Vivekanandan Shanmuganathan, Amma A Semenya, Elizabeth Sweeney, Katherine Paul, Evan W Secor, Ruth M RuprechtAbstract:Background The high prevalence of HIV-1/AIDS in areas endemic for schistosomiasis and other helminthic infections has led to the hypothesis that parasites increase Host Susceptibility to immunodeficiency virus infection. We previously showed that rhesus macaques (RM) with active schistosomiasis were significantly more likely to become systemically infected after intrarectal (i.r.) exposure to an R5-tropic clade C simian-human immunodeficiency virus (SHIV-C) than were parasite-free controls. However, we could not address whether this was due to systemic or mucosal effects. If systemic immunoactivation resulted in increased Susceptibility to SHIV-C acquisition, a similarly large difference in Host Susceptibility would be seen after intravenous (i.v.) SHIV-C challenge. Conversely, if increased Host Susceptibility was due to parasite-induced immunoactivation at the mucosal level, i.v. SHIV-C challenge would not result in significant differences between parasitized and parasite-free monkeys. Methods and Findings We enrolled two groups of RM and infected one group with Schistosoma mansoni; the other group was left parasite-free. Both groups were challenged i.v. with decreasing doses of SHIV-C. No statistically significant differences in 50% animal infectious doses (AID50) or peak viremia were seen between the two groups. These data strongly contrast the earlier i.r. SHIV-C challenge (using the same virus stock) in the presence/absence of parasites, where we noted a 17-fold difference in AID50 and one log higher peak viremia in parasitized monkeys (P<0.001 for both). The lack of significant differences after the i.v. challenge implies that the increased Host Susceptibility is predominantly due to parasite-mediated mucosal upregulation of virus replication and spread, rather than systemic effects. Conclusions The major impact of schistosome-induced increased Host Susceptibility is at the mucosal level. Given that >90% of all new HIV-1 infections worldwide are acquired through mucosal contact, parasitic infections that inflame mucosae may play an important role in the spread of HIV-1.
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Schistosoma mansoni Enhances Host Susceptibility to Mucosal but Not Intravenous Challenge by R5 Clade C SHIV
PLOS Neglected Tropical Diseases, 2011Co-Authors: Nagadenahalli B Siddappa, Girish Hemashettar, Vivekanandan Shanmuganathan, Amma A Semenya, Elizabeth Sweeney, Katherine Paul, W. Evan Secor, Ruth M RuprechtAbstract:Background The high prevalence of HIV-1/AIDS in areas endemic for schistosomiasis and other helminthic infections has led to the hypothesis that parasites increase Host Susceptibility to immunodeficiency virus infection. We previously showed that rhesus macaques (RM) with active schistosomiasis were significantly more likely to become systemically infected after intrarectal (i.r.) exposure to an R5-tropic clade C simian-human immunodeficiency virus (SHIV-C) than were parasite-free controls. However, we could not address whether this was due to systemic or mucosal effects. If systemic immunoactivation resulted in increased Susceptibility to SHIV-C acquisition, a similarly large difference in Host Susceptibility would be seen after intravenous (i.v.) SHIV-C challenge. Conversely, if increased Host Susceptibility was due to parasite-induced immunoactivation at the mucosal level, i.v. SHIV-C challenge would not result in significant differences between parasitized and parasite-free monkeys. Methods and Findings We enrolled two groups of RM and infected one group with Schistosoma mansoni; the other group was left parasite-free. Both groups were challenged i.v. with decreasing doses of SHIV-C. No statistically significant differences in 50% animal infectious doses (AID50) or peak viremia were seen between the two groups. These data strongly contrast the earlier i.r. SHIV-C challenge (using the same virus stock) in the presence/absence of parasites, where we noted a 17-fold difference in AID50 and one log higher peak viremia in parasitized monkeys (P90% of all new HIV-1 infections worldwide are acquired through mucosal contact, parasitic infections that inflame mucosae may play an important role in the spread of HIV-1.
B Boag - One of the best experts on this subject based on the ideXlab platform.
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variation in Host Susceptibility and infectiousness generated by co infection the myxoma tricHostrongylus retortaeformis case in wild rabbits
Journal of the Royal Society Interface, 2007Co-Authors: Isabella M Cattadori, Reka Albert, B BoagAbstract:One of the conditions that can affect Host Susceptibility and parasite transmission is the occurrence of concomitant infections. Parasites interact directly or indirectly within an individual Host and often these interactions are modulated by the Host immune response. We used a free-living rabbit population co-infected with the nematode TricHostrongylus retortaeformis, which appears to stimulate an acquired immune response, and the immunosuppressive poxvirus myxoma. Modelling was used to examine how myxoma infection alters the immune-mediated establishment and death/expulsion of T. retortaeformis, and consequently affects parasite intensity and duration of the infection. Simulations were based on the general TH1–TH2 immunological paradigm that proposes the polarization of the Host immune response towards one of the two subsets of T helper cells. Our findings suggest that myxoma infections contribute to alter Host Susceptibility to the nematode, as co-infected rabbits showed higher worm intensity compared with virus negative Hosts. Results also suggest that myxoma disrupts the ability of the Host to clear T. retortaeformis as worm intensities were consistently high and remained high in old rabbits. However, the co-infection model has to include some immune-mediated nematode regulation to be consistent with field data, indicating that the TH1–TH2 dichotomy is not complete. We conclude that seasonal myxoma outbreaks enhance Host Susceptibility to the nematode and generate highly infected Hosts that remain infectious for a longer time. Finally, the virus–nematode co-infection increases heterogeneities among individuals and potentially has a large effect on parasite transmission.
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Variation in Host Susceptibility and infectiousness generated by co-infection: the myxoma–TricHostrongylus retortaeformis case in wild rabbits
Journal of the Royal Society Interface, 2007Co-Authors: Isabella M Cattadori, Reka Albert, B BoagAbstract:One of the conditions that can affect Host Susceptibility and parasite transmission is the occurrence of concomitant infections. Parasites interact directly or indirectly within an individual Host and often these interactions are modulated by the Host immune response. We used a free-living rabbit population co-infected with the nematode TricHostrongylus retortaeformis, which appears to stimulate an acquired immune response, and the immunosuppressive poxvirus myxoma. Modelling was used to examine how myxoma infection alters the immune-mediated establishment and death/expulsion of T. retortaeformis, and consequently affects parasite intensity and duration of the infection. Simulations were based on the general TH1–TH2 immunological paradigm that proposes the polarization of the Host immune response towards one of the two subsets of T helper cells. Our findings suggest that myxoma infections contribute to alter Host Susceptibility to the nematode, as co-infected rabbits showed higher worm intensity compared with virus negative Hosts. Results also suggest that myxoma disrupts the ability of the Host to clear T. retortaeformis as worm intensities were consistently high and remained high in old rabbits. However, the co-infection model has to include some immune-mediated nematode regulation to be consistent with field data, indicating that the TH1–TH2 dichotomy is not complete. We conclude that seasonal myxoma outbreaks enhance Host Susceptibility to the nematode and generate highly infected Hosts that remain infectious for a longer time. Finally, the virus–nematode co-infection increases heterogeneities among individuals and potentially has a large effect on parasite transmission.
David Ginsburg - One of the best experts on this subject based on the ideXlab platform.
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reduced thrombin generation increases Host Susceptibility to group a streptococcal infection
Blood, 2009Co-Authors: Xixi Wang, David Ginsburg, Jay L DegenAbstract:Bacterial plasminogen activators are commonplace among microbial pathogens, implying a central role of Host plasmin in supporting bacterial virulence. Group A streptococci (GAS) secrete streptokinase, a specific activator of human plasminogen (PLG). The critical contribution of the streptokinase-PLG interaction to GAS pathogenicity was recently demonstrated using mice expressing human PLG. To examine the importance of thrombin generation in antimicrobial Host defense, we challenged mice with deficiency of factor V (FV) in either the plasma or platelet compartment. Reduction of FV in either pool resulted in markedly increased mortality after GAS infection, with comparison to heterozygous F5-deficient mice suggesting a previously unappreciated role for the platelet FV pool in Host defense. Mice with complete deficiency of fibrinogen also demonstrated markedly increased mortality to GAS infection relative to controls. Although FV Leiden may be protective in the setting of severe sepsis in humans, no significant survival advantage was observed in GAS-infected mice carrying the FV Leiden mutation. Taken together, our data support the hypothesis that local thrombosis/fibrin deposition limits the survival and dissemination of at least a subset of microbial pathogens and suggest that common variation in hemostatic factors among humans could affect Host Susceptibility to a variety of infectious diseases.
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Factor V Level Affects the Host Susceptibility to Group A Streptococcal Infection.
Blood, 2005Co-Authors: Angela Yang, Xixi Wang, David GinsburgAbstract:Group A streptococci (GAS), a common human pathogen, secrete streptokinase (SK), which activates the Host’s plasminogen (PLG). SK is highly specific for human PLG, exhibiting little or no activity against other mammalian species. We demonstrated the major role of the PLG/SK interaction in GAS pathogenicity using a transgenic murine model expressing human plasminogen with increased Susceptibility to human pathogenic streptococci. We hypothesize that GAS hijack the Host fibrinolytic system in order to circumvent local thrombosis for systemic spread. Markedly increased mortality was also observed following GAS injection in C57BL/6J mice treated with the snake venom Ancrod, which proteolytically degrades plasma fibrinogen, supporting the critical roles of coagulation in Host/pathogen interaction. However, fibrinogen also plays important roles in inflammation and immune response, it is necessary to use independent genetic models to further test the impact of coagulation in Host defense against bacterial infection. The effect of variations in FV on mouse Susceptibility to streptococcal infection was tested. We established a mouse model with low plasma FV level. These mice have a slightly increased bleeding time, though otherwise phenotypically normal. Subjected to streptococcal infection, these mice exhibited significantly increased mortality than wildtype controls, suggesting that the decreased thrombotic tendency in the low FV mice increases Host Susceptibility to infection. FV Leiden is a common prothrombotic mutation among Caucasian population with an incidence between 4% and 6%. Previous studies from Kerlin et al demonstrated the FV Leiden conferred survival advantage in patients with severe sepsis and in mice challenged with endotoxin. This may be an example of balanced gene polymorphism that maintains the FV Leiden mutant in the general gene pool by selection of bacterial infections. In order to identify the selective agents responsible for the prevalence of FV Leiden mutation, we took advantage of our plasminogen transgenic murine model for streptococcal infection to test whether streptococci is one of the selective agents. Human plasminogen transgene was introduced into FV Leiden background and the Susceptibility to streptococcal infection was measured. No significant improvement of survival was observed in the FV Leiden mouse comparing with the wildtype control. Thus, streptococcal infection is not the selective agent for the prevalence of FV Leiden mutation. These observations highlight the potential role of variations in blood coagulation factors in Host Susceptibility to bacterial infection.
Henry L Schreiber - One of the best experts on this subject based on the ideXlab platform.
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bacterial virulence phenotypes of escherichia coli and Host Susceptibility determine risk for urinary tract infections
Science Translational Medicine, 2017Co-Authors: Henry L Schreiber, Matt S Conover, Wenchi Chou, Michael E Hibbing, Abigail L Manson, Karen W Dodson, Thomas J Hannan, Pacita L Roberts, Ann E StapletonAbstract:Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in their urovirulence, that is, their ability to infect the bladder in a mouse model of cystitis. We found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the E. coli strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and metabolism, could be used to predict subsequent colonization of the mouse bladder. Together, our findings suggest that UTI risk and outcome may be determined by complex interactions between Host Susceptibility and the urovirulence potential of diverse bacterial strains.
