Interleukin-9 enhances resistance to the intestinal nematode Trichuris muris.
Upon infection with the cecum-dwelling nematode Trichuris muris, the majority of inbred strains of mice launch a Th2-type immune response and in doing so expel the parasite before patency. In contrast, there are a few mouse strains which develop a nonprotective Th1-type response resulting in a chronic infection and the presence of adult worms. Of the Th2 cytokines known to be associated with the resistant phenotype (interleukin-4 [IL-4], IL-5, IL-9, and IL-13), comparatively little is known about the contribution that IL-9 makes towards the protective immune response. In this study we demonstrate that IL-9 is expressed early during the Th2-type response and that its elevation in vivo results in the enhancement of intestinal mastocytosis and the production of both the immunoglobulin E (IgE) and IgG1 isotypes. In addition, elevated IL-9 levels in vivo facilitated the loss of T. muris from the intestine. That IL-9 is important in promoting worm expulsion was also seen following infection of IL-9-transgenic mice, which constitutively overexpress the cytokine. These animals displayed an extremely rapid, but immune mediated, expulsion of the parasite. Also evident in these animals was a pronounced intestinal mastocytosis, which was previously shown by us to be responsible for the expulsion of the related nematode Trichinella spiralis from these animals. Taken together with observations of IL-9 production following infection with other helminths, the results imply that IL-9 contributes to the general mast cell and IgE response characteristic of these infections and, more specifically, enhances resistance to T. muris.
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom. H.Faulkner@biosci.salfcrd.ac.uk
H
H
Faulkner
J C
JC
Renauld
J
J
Van Snick
R K
RK
Grencis
D000818:Animals; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D007113:Immunity, Innate / Q000276:immunology; D016906:Interleukin-9 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018418:Th2 Cells / Q000276:immunology; D014257:Trichuriasis / Q000276:immunology* / Q000378:metabolism; D014258:Trichuris / Q000276:immunology*
D016906:Interleukin-9