The Experts below are selected from a list of 21927 Experts worldwide ranked by ideXlab platform
Mary M Stevenson - One of the best experts on this subject based on the ideXlab platform.
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reduced protective efficacy of a blood stage malaria vaccine by concurrent Nematode Infection
Infection and Immunity, 2006Co-Authors: Zhong Su, Mariela Segura, Mary M StevensonAbstract:Helminth Infections, which are prevalent in areas where malaria is endemic, have been shown to modulate immune responses to unrelated pathogens and have been implicated in poor efficacy of malaria vaccines in humans. We established a murine coInfection model involving blood-stage Plasmodium chabaudi AS malaria and a gastrointestinal Nematode, Heligmosomoides polygyrus, to investigate the impact of Nematode Infection on the protective efficacy of a malaria vaccine. C57BL/6 mice immunized with crude blood-stage P. chabaudi AS antigen in TiterMax adjuvant developed strong protection against malaria challenge. The same immunization protocol failed to induce strong protection in H. polygyrus-infected mice. Immunized Nematode-infected mice produced significantly lower levels of malaria-specific antibody than Nematode-free mice produced. In response to Nematode and malarial antigens, spleen cells from immunized Nematode-infected mice produced significantly lower levels of gamma interferon but more interleukin-4 (IL-4), IL-13, and IL-10 in vitro than spleen cells from immunized Nematode-free mice produced. Furthermore, H. polygyrus Infection also induced a strong transforming growth factor β1 response in vivo and in vitro. Deworming treatment of H. polygyrus-infected mice before antimalarial immunization, but not deworming treatment after antimalarial immunization, restored the protective immunity to malaria challenge. These results demonstrate that concurrent Nematode Infection strongly modulates immune responses induced by an experimental malaria vaccine and consequently suppresses the protective efficacy of the vaccine against malaria challenge.
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impairment of protective immunity to blood stage malaria by concurrent Nematode Infection
Infection and Immunity, 2005Co-Authors: Zhong Su, Mariela Segura, Mary M Stevenson, Kenneth Morgan, Concepcion J LoredoostiAbstract:Helminthiases, which are highly prevalent in areas where malaria is endemic, have been shown to modulate or suppress the immune response to unrelated antigens or pathogens. In this study, we established a murine model of coInfection with a gastrointestinal Nematode parasite, Heligmosomoides polygyrus, and the blood-stage malaria parasite Plasmodium chabaudi AS in order to investigate the modulation of antimalarial immunity by concurrent Nematode Infection. Chronic Infection with the Nematode for 2, 3, or 5 weeks before P. chabaudi AS Infection severely impaired the ability of C57BL/6 mice to control malaria, as demonstrated by severe mortality and significantly increased malaria peak parasitemia levels. Coinfected mice produced significantly lower levels of gamma interferon (IFN-γ) during P. chabaudi AS Infection than mice infected with malaria alone. Concurrent Nematode Infection also suppressed production of type 1-associated, malaria-specific immunoglobulin G2a. Mice either infected with the Nematode alone or coinfected with the Nematode and malaria had high transforming growth factor β1 (TGF-β1) levels, and concurrent Nematode and malaria Infections resulted in high levels of interleukin-10 in vivo. Splenic CD11c+ dendritic cells (DC) from mice infected with malaria alone and coinfected mice showed similarly increased expression of CD40, CD80, and CD86, but DC from coinfected mice were unable to induce CD4+ T-cell proliferation and optimal IFN-γ production in response to the malaria antigen in vitro. Importantly, treatment of Nematode-infected mice with an anthelmintic drug prior to malaria Infection fully restored protective antimalarial immunity and reduced TGF-β1 levels. These results demonstrate that concurrent Nematode Infection strongly modulates multiple aspects of immunity to blood-stage malaria and consequently impairs the development of protective antimalarial immunity.
Richard K Grencis - One of the best experts on this subject based on the ideXlab platform.
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manipulation of host and parasite microbiotas survival strategies during chronic Nematode Infection
Science Advances, 2018Co-Authors: Emily C White, Ashley Houlden, Allison J Bancroft, Kelly S Hayes, Marie Goldrick, Richard K Grencis, Ian S D RobertsAbstract:Intestinal dwelling parasites have evolved closely with the complex intestinal microbiota of their host, but the significance of the host microbiota for metazoan pathogens and the role of their own intestinal microbiota are still not fully known. We have found that the parasitic Nematode Trichuris muris acquired a distinct intestinal microbiota from its host, which was required for Nematode fitness. Infection of germ-free mice and mice monocolonized with Bacteroides thetaiotaomicron demonstrated that successful T. muris Infections require a host microbiota. Following Infection, T. muris –induced alterations in the host intestinal microbiota inhibited subsequent rounds of Infection, controlling parasite numbers within the host intestine. This dual strategy could promote the long-term survival of the parasite within the intestinal niche necessary for successful chronic Nematode Infection.
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mucin gene deficiency in mice impairs host resistance to an enteric parasitic Infection
Gastroenterology, 2010Co-Authors: Sumaira Z Hasnain, Yikang Deng, Richard K Grencis, Huaqing Wang, Jeaneric Ghia, Nihal Haq, Anna Velcich, David J Thornton, Waliul I KhanAbstract:Background & Aims Hyperplasia of mucin-secreting intestinal goblet cells accompanies a number of enteric Infections, including Infections by Nematode parasites. Nevertheless, the precise role of mucins in host defense in Nematode Infection is not known. We investigated the role of the mucin (Muc2) in worm expulsion and host immunity in a model of Nematode Infection. Methods Resistant (BALB/c, C57BL/6), susceptible (AKR), and Muc2-deficient mouse strains were infected with the Nematode, Trichuris muris , and worm expulsion, energy status of the whipworms, changes in mucus/mucins, and inflammatory and immune responses were investigated after Infection. Results The increase in Muc2 production, observed exclusively in resistant mice, correlated with worm expulsion. Moreover, expulsion of the worms from the intestine was significantly delayed in the Muc2-deficient mice. Although a marked impairment in the development of periodic acid Schiff (PAS)–stained intestinal goblet cells was observed in Muc2-deficient mice, as Infection progressed a significant increase in the number of PAS-positive goblet cells was observed in these mice. Surprisingly, an increase in Muc5ac, a mucin normally expressed in the airways and stomach, was observed after Infection of only the resistant animals. Overall, the mucus barrier in the resistant mice was less permeable than that of susceptible mice. Furthermore, the worms isolated from the resistant mice had a lower energy status. Conclusions Mucins are an important component of innate defense in enteric Infection; this is the first demonstration of the important functional contribution of mucins to host protection from Nematode Infection.
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intraepithelial nk cell derived il 13 induces intestinal pathology associated with Nematode Infection
Journal of Immunology, 2005Co-Authors: Jacqueline R Mcdermott, Neil E Humphreys, Simon P Forman, Debra D Donaldson, Richard K GrencisAbstract:IL-13 is a Th2-derived cytokine associated with pathological changes in asthma and ulcerative colitis. Moreover, it plays a major role in the control of gut Nematode Infection and associated immunopathology. The current paradigm is that these effects are due to T cell-derived IL-13. We show in this study that an innate source of IL-13, the intraepithelial NK cell, is responsible for the disruption of intestinal tissue architecture and induction of goblet cell hyperplasia that characterizes Infection with the intestinal helminth Trichinella spiralis. IL-13 or IL-4Ralpha (but not IL-4) null mice failed to induce intestinal pathology. Unexpectedly, SCID and athymic mice developed the same pathology found in immunocompetent mice following Infection. Moreover, immunodeficient mice expressed IL-13 in the intestine, and abnormal mucosal pathology was reduced by in vivo administration of a soluble IL-13 antagonist. IL-13 expression was induced in non-T intraepithelial CD3- NK cells. Epithelial cells expressed the IL-13 signaling receptor, IL-13Ralpha1, and after Infection, IL-4Ralpha. Furthermore, the soluble IL-13 decoy receptor IL-13Ralpha2, which regulates IL-13 responses, was also induced upon Infection. These data provide the first evidence that intestinal tissue restructuring during helminth Infection is an innate event dependent on IL-13 production by NK cells resident in the epithelium of the intestine.
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wsx 1 a key role in induction of chronic intestinal Nematode Infection
Journal of Immunology, 2004Co-Authors: Allison J Bancroft, Neil E Humphreys, John J Worthington, Hiroki Yoshida, Richard K GrencisAbstract:Chronic Infection by the gastrointestinal Nematode Trichuris muris in susceptible AKR mice, which mount a Th1 response, is associated with IL-27p28 expression in the cecum. In contrast to wild-type mice, mice that lack the WSX-1/IL-27R gene fail to harbor a chronic Infection, having significantly lower Th1 responses. The lower level of Ag-specific IFN-gamma-positive cells in WSX-1 knockout (KO) mice was found to be CD4(+) T cell specific, and the KO mice also had increased levels of IL-4-positive CD4(+) T cells. Polyclonal activation of mesenteric lymph node cells from naive WSX-1 KO or wild-type mice demonstrated that there was no inherent defect in the production of IFN-gamma by CD4(+) T cells, suggesting the decrease in these cells seen in infected WSX-1 KO mice is an in vivo Ag-driven effect. IL-12 treatment of WSX-1 KO mice failed to rescue the type 1 response, resulting in unaltered type-2-driven resistance. Infection of WSX-1 KO mice was also associated with a reduction of IL-27/WSX-1 downstream signaling gene expression within the cecum. These studies demonstrate an important role for WSX-1 signaling in the promotion of type 1 responses and chronic gastrointestinal Nematode Infection.
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essential role for tlr4 and myd88 in the development of chronic intestinal Nematode Infection
European Journal of Immunology, 2003Co-Authors: Helena Helmby, Richard K GrencisAbstract:Expulsion of the gastrointestinal Nematode Trichuris muris is mediated by a T helper 2 type response involving IL-4 and IL-13. Here we show that Th1 response-associated susceptibility is dependent on activation signals mediated by MyD88 and Toll-like receptor 4 (TLR4). TLR4- and MyD88-deficient mice are highly resistant to chronic T. muris Infection and develop strong antigen-specific Th2 responses in mucosa-associated lymphoid tissues. Hence, TLR4 and MyD88 are involved not only in the development of pro-inflammatory responses against bacterial pathogens but are also crucially involved in responses against multicellular organisms such as helminths. These results provide the first demonstration of the critical role of TLR4 and MyD88 in bridging the innate and acquired immune response during gastrointestinal Nematode Infection.
Zhong Su - One of the best experts on this subject based on the ideXlab platform.
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reduced protective efficacy of a blood stage malaria vaccine by concurrent Nematode Infection
Infection and Immunity, 2006Co-Authors: Zhong Su, Mariela Segura, Mary M StevensonAbstract:Helminth Infections, which are prevalent in areas where malaria is endemic, have been shown to modulate immune responses to unrelated pathogens and have been implicated in poor efficacy of malaria vaccines in humans. We established a murine coInfection model involving blood-stage Plasmodium chabaudi AS malaria and a gastrointestinal Nematode, Heligmosomoides polygyrus, to investigate the impact of Nematode Infection on the protective efficacy of a malaria vaccine. C57BL/6 mice immunized with crude blood-stage P. chabaudi AS antigen in TiterMax adjuvant developed strong protection against malaria challenge. The same immunization protocol failed to induce strong protection in H. polygyrus-infected mice. Immunized Nematode-infected mice produced significantly lower levels of malaria-specific antibody than Nematode-free mice produced. In response to Nematode and malarial antigens, spleen cells from immunized Nematode-infected mice produced significantly lower levels of gamma interferon but more interleukin-4 (IL-4), IL-13, and IL-10 in vitro than spleen cells from immunized Nematode-free mice produced. Furthermore, H. polygyrus Infection also induced a strong transforming growth factor β1 response in vivo and in vitro. Deworming treatment of H. polygyrus-infected mice before antimalarial immunization, but not deworming treatment after antimalarial immunization, restored the protective immunity to malaria challenge. These results demonstrate that concurrent Nematode Infection strongly modulates immune responses induced by an experimental malaria vaccine and consequently suppresses the protective efficacy of the vaccine against malaria challenge.
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impairment of protective immunity to blood stage malaria by concurrent Nematode Infection
Infection and Immunity, 2005Co-Authors: Zhong Su, Mariela Segura, Mary M Stevenson, Kenneth Morgan, Concepcion J LoredoostiAbstract:Helminthiases, which are highly prevalent in areas where malaria is endemic, have been shown to modulate or suppress the immune response to unrelated antigens or pathogens. In this study, we established a murine model of coInfection with a gastrointestinal Nematode parasite, Heligmosomoides polygyrus, and the blood-stage malaria parasite Plasmodium chabaudi AS in order to investigate the modulation of antimalarial immunity by concurrent Nematode Infection. Chronic Infection with the Nematode for 2, 3, or 5 weeks before P. chabaudi AS Infection severely impaired the ability of C57BL/6 mice to control malaria, as demonstrated by severe mortality and significantly increased malaria peak parasitemia levels. Coinfected mice produced significantly lower levels of gamma interferon (IFN-γ) during P. chabaudi AS Infection than mice infected with malaria alone. Concurrent Nematode Infection also suppressed production of type 1-associated, malaria-specific immunoglobulin G2a. Mice either infected with the Nematode alone or coinfected with the Nematode and malaria had high transforming growth factor β1 (TGF-β1) levels, and concurrent Nematode and malaria Infections resulted in high levels of interleukin-10 in vivo. Splenic CD11c+ dendritic cells (DC) from mice infected with malaria alone and coinfected mice showed similarly increased expression of CD40, CD80, and CD86, but DC from coinfected mice were unable to induce CD4+ T-cell proliferation and optimal IFN-γ production in response to the malaria antigen in vitro. Importantly, treatment of Nematode-infected mice with an anthelmintic drug prior to malaria Infection fully restored protective antimalarial immunity and reduced TGF-β1 levels. These results demonstrate that concurrent Nematode Infection strongly modulates multiple aspects of immunity to blood-stage malaria and consequently impairs the development of protective antimalarial immunity.
Susanne Hartmann - One of the best experts on this subject based on the ideXlab platform.
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Table_2_A Novel Non-invasive Method to Detect RELM Beta Transcript in Gut Barrier Related Changes During a Gastrointestinal Nematode Infection.XLSX
2019Co-Authors: Norus Ahmed, Anja A Kuhl, Emanuel Heitlinger, Nicole Affinass, Natasa Xenophontos, Victor Hugo Jarquin, Jenny Jost, Svenja Steinfelder, Susanne HartmannAbstract:Currently, methods for monitoring changes of gut barrier integrity and the associated immune response via non-invasive means are limited. Therefore, we aimed to develop a novel non-invasive technique to investigate immunological host responses representing gut barrier changes in response to Infection. We identified the mucous layer on feces from mice to be mainly composed of exfoliated intestinal epithelial cells. Expression of RELM-β, a gene prominently expressed in intestinal Nematode Infections, was used as an indicator of intestinal cellular barrier changes to Infection. RELM-β was detected as early as 6 days post-Infection (dpi) in exfoliated epithelial cells. Interestingly, RELM-β expression also mirrored the quality of the immune response, with higher amounts being detectable in a secondary Infection and in high dose Nematode Infection in laboratory mice. This technique was also applicable to captured worm-infected wild house mice. We have therefore developed a novel non-invasive method reflecting gut barrier changes associated with alterations in cellular responses to a gastrointestinal Nematode Infection.
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Video_1_A Novel Non-invasive Method to Detect RELM Beta Transcript in Gut Barrier Related Changes During a Gastrointestinal Nematode Infection.MP4
2019Co-Authors: Norus Ahmed, Anja A Kuhl, Emanuel Heitlinger, Nicole Affinass, Natasa Xenophontos, Victor Hugo Jarquin, Jenny Jost, Svenja Steinfelder, Susanne HartmannAbstract:Currently, methods for monitoring changes of gut barrier integrity and the associated immune response via non-invasive means are limited. Therefore, we aimed to develop a novel non-invasive technique to investigate immunological host responses representing gut barrier changes in response to Infection. We identified the mucous layer on feces from mice to be mainly composed of exfoliated intestinal epithelial cells. Expression of RELM-β, a gene prominently expressed in intestinal Nematode Infections, was used as an indicator of intestinal cellular barrier changes to Infection. RELM-β was detected as early as 6 days post-Infection (dpi) in exfoliated epithelial cells. Interestingly, RELM-β expression also mirrored the quality of the immune response, with higher amounts being detectable in a secondary Infection and in high dose Nematode Infection in laboratory mice. This technique was also applicable to captured worm-infected wild house mice. We have therefore developed a novel non-invasive method reflecting gut barrier changes associated with alterations in cellular responses to a gastrointestinal Nematode Infection.
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Image_1_A Novel Non-invasive Method to Detect RELM Beta Transcript in Gut Barrier Related Changes During a Gastrointestinal Nematode Infection.TIF
2019Co-Authors: Norus Ahmed, Anja A Kuhl, Emanuel Heitlinger, Nicole Affinass, Natasa Xenophontos, Victor Hugo Jarquin, Jenny Jost, Svenja Steinfelder, Susanne HartmannAbstract:Currently, methods for monitoring changes of gut barrier integrity and the associated immune response via non-invasive means are limited. Therefore, we aimed to develop a novel non-invasive technique to investigate immunological host responses representing gut barrier changes in response to Infection. We identified the mucous layer on feces from mice to be mainly composed of exfoliated intestinal epithelial cells. Expression of RELM-β, a gene prominently expressed in intestinal Nematode Infections, was used as an indicator of intestinal cellular barrier changes to Infection. RELM-β was detected as early as 6 days post-Infection (dpi) in exfoliated epithelial cells. Interestingly, RELM-β expression also mirrored the quality of the immune response, with higher amounts being detectable in a secondary Infection and in high dose Nematode Infection in laboratory mice. This technique was also applicable to captured worm-infected wild house mice. We have therefore developed a novel non-invasive method reflecting gut barrier changes associated with alterations in cellular responses to a gastrointestinal Nematode Infection.
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small intestinal Nematode Infection of mice is associated with increased enterobacterial loads alongside the intestinal tract
PLOS ONE, 2013Co-Authors: Sebastian Rausch, Josephin Held, Andre Fischer, Markus M Heimesaat, Anja A Kuhl, Stefan Bereswill, Susanne HartmannAbstract:Parasitic Nematodes are potent modulators of immune reactivity in mice and men. Intestinal Nematodes live in close contact with commensal gut bacteria, provoke biased Th2 immune responses upon Infection, and subsequently lead to changes in gut physiology. We hypothesized that murine Nematode Infection is associated with distinct changes of the intestinal bacterial microbiota composition. We here studied intestinal inflammatory and immune responses in mice following Infection with the hookworm Heligmosomoidespolygyrusbakeri and applied cultural and molecular techniques to quantitatively assess intestinal microbiota changes in the ileum, cecum and colon. At day 14 post Nematode Infection, mice harbored significantly higher numbers of γ-Proteobacteria/Enterobacteriaceae and members of the Bacteroides/Prevotella group in their cecum as compared to uninfected controls. Abundance of Gram-positive species such as Lactobacilli, Clostridia as well as the total bacterial load was not affected by worm Infection. The altered microbiota composition was independent of the IL-4/-13 – STAT6 signaling axis, as infected IL-4Rα-/- mice showed a similar increase in enterobacterial loads. In conclusion, Infection with an enteric Nematode is accompanied by distinct intestinal microbiota changes towards higher abundance of gram-negative commensal species at the small intestinal site of Infection (and inflammation), but also in the parasite-free large intestinal tract. Further studies should unravel the impact of Nematode-induced microbiota changes in inflammatory bowel disease to allow for a better understanding of how theses parasites interfere with intestinal inflammation and bacterial communities in men.
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a matter of timing early not chronic phase intestinal Nematode Infection restrains control of a concurrent enteric protozoan Infection
European Journal of Immunology, 2010Co-Authors: Sebastian Rausch, Josephin Held, Joerg Stange, Matthias Lendner, Matthew R Hepworth, Christian Klotz, Richard Lucius, Thomas Pogonka, Susanne HartmannAbstract:Infections with parasitic worms are often long lasting and associated with modulated immune responses. We analyzed the influence of the Nematode Heligmosomoides polygyrus bakeri dwelling in the small intestine on concurrent protozoan Infection with Eimeria falciformis residing in the cecum. To dissect the effects of a Nematode Infection in the early versus chronic phase, we infected animals with E. falciformis 6 or 28 days post H. p. bakeri Infection. Only a concurrent early Nematode Infection led to an increased replication of the protozoan parasite, whereas a chronic worm Infection had no influence on the control of E. falciformis. Increased protozoan replication correlated with the reduced production of IFN-γ, IL-12/23, CCL4, CXCL9 and CXCL10, reduced migration of T cells and increased expression of Foxp3 at the site of protozoan Infection. This was accompanied by a stronger Nematode-specific Th2 response in gut-draining LN. Protection of mice against challenge Infections with the protozoan parasite was not altered. Hence, the detrimental effect of a Nematode Infection on the control of a concurrent protozoan Infection is transient and occurs only in the narrow time window of the early phase of Infection.
Amy B Pedersen - One of the best experts on this subject based on the ideXlab platform.
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experimental parasite community perturbation reveals associations between sin nombre virus and gastrointestinal Nematodes in a rodent reservoir host
Biology Letters, 2020Co-Authors: Amy R Sweeny, Courtney A Thomason, Edwin A Carbajal, Christina Hansen, Andrea L Graham, Amy B PedersenAbstract:Individuals are often co-infected with several parasite species, yet measuring within-host interactions remains difficult in the wild. Consequently, the impacts of such interactions on host fitness and epidemiology are often unknown. We used anthelmintic drugs to experimentally reduce Nematode Infection and measured the effects on both Nematodes and the important zoonosis Sin Nombre virus (SNV) in its primary reservoir (Peromyscus spp.). Treatment significantly reduced Nematode Infection, but increased SNV seroprevalence. Furthermore, mice that were co-infected with both Nematodes and SNV were in better condition and survived up to four times longer than uninfected or singly infected mice. These results highlight the importance of investigating multiple parasites for understanding interindividual variation and epidemiological dynamics in reservoir populations with zoonotic transmission potential.
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experimental parasite community perturbation reveals associations between sin nombre virus and gastrointestinal Nematodes in a rodent reservoir host
bioRxiv, 2020Co-Authors: Amy R Sweeny, Courtney A Thomason, Edwin A Carbajal, Christina Hansen, Andrea L Graham, Amy B PedersenAbstract:Abstract Individuals are often co-infected with several parasite species, yet measuring within-host interactions remains difficult in the wild. Consequently, such interactions’ impacts on host fitness and epidemiology are often unknown. We used anthelmintic drugs to experimentally reduce Nematode Infection and measured the effects on both Nematodes and the important zoonosis Sin Nombre virus (SNV) in its primary wild reservoir (Peromyscus spp.). Treatment significantly reduced Nematode Infection, but increased SNV seroprevalence. Furthermore, mice that were co-infected with both Nematodes and SNV were in better condition and survived as much as four times longer than mice infected with either parasite alone. These results highlight the importance of investigating multiple parasites for understanding interindividual variation and epidemiological dynamics in reservoir populations with zoonotic transmission potential.
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anthelmintic treatment alters the parasite community in a wild mouse host
Biology Letters, 2013Co-Authors: Amy B Pedersen, Janis AntonovicsAbstract:Individuals are often co-infected with several parasite species, yet the consequences of drug treatment on the dynamics of parasite communities in wild populations have rarely been measured. Here, we experimentally reduced Nematode Infection in a wild mouse population and measured the effects on other non-target parasites. A single oral dose of the anthelmintic, ivermectin, significantly reduced Nematode Infection, but resulted in a reciprocal increase in other gastrointestinal parasites, specifically coccidial protozoans and cestodes. These results highlight the possibility that drug therapy may have unintended consequences for non-target parasites and that host–parasite dynamics cannot always be fully understood in the framework of single host–parasite interactions.
