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Title: the role of eosinophils in regulation of T- and B-cell responses during enteric nematode infection
Background: eosinophils are implicated in B-cell maintenance and Th2 induction and are increasingly recognized for their influence on the development of Peyer’s patches (PP). Moreover, it was recently discovered that eosinophils support IgA class switching in the PP, further implicating eosinophils in intestinal homeostasis. However, whether the PP participate in immune responses against intestinal helminths and whether eosinophils influences such responses has not been studied. Here eosinophil deficient mice were used to investigate the role of eosinophils in intestinal Th2 responses, using the small intestinal nematode Heligmosomoides polygyrus- a natural pathogen of mice and a useful model for human gastrointestinal helminth infection, but to which the role of eosinophils in host protection is understudied.
1. Determine whether the PP participate in H. polygyrus induced Th2 and antibody responses.
2. Determine whether eosinophils affect Th2 and antibody responses to H. polygyrus
3. Assess whether eosinophil deficiency affects the survival and fecundity of H. polygyrus.
Results: the main immune response to H. polygyrus in wild type (WT) mice was found to take place in the gut-draining mesenteric lymph nodes (mLN), not the PP and eosinophils were found to maintain a divison of labor between the PP and mLN. Specifically, whereas H. polygyrus infection did not result in significant increases of IL-4+ T-cells or IgG1+ B-cells in the PP of WT mice, significant increases in IL-4+ and IgG1+ cells were detected in the PP of eosinophil deficient mice. This was despite Th2 induction and IgG1 class switching being unaffected by eosinophil deficiency in the mLN. The increase of IL-4 producing cells in the PP of eosinophil deficient mice was specifically evident in T-follicular helper cells (TFH), whereas TFH in PP of WT mice did not increase IL-4 production in response to H. polygyrus. The PP of WTmice maintained high levels of IgA production following H. polygyrus infection, Whereas the frequencies of IgA+ B-cells dropped considerably in the PP of infected eosinophil-deficient mice. Finally, although H. polygyrus survival was not affected by the absence of eosinophils, eosinophil deficiency significantly impaired parasite fecundity. this was despite expression of molecules with known anti-helminth functions being comparable between eosinophil deficient and wt mice.
conclusion: this work demonstrates that eosinohils maintain a regulated state in the pp during infection with h. polygyrus. this places the eosinophil in a new, evolutionary sensible position in which it ensures that iga production is maintained despite infection with an enteric pathogen.