IL-1-dependent, IL-1R1-independent resistance to gastrointestinal nematodes.
IL-1 null mice are unable to expel the intestinal nematode Trichuris muris; whereas WT littermates exhibit sterile immunity. Intriguingly the essential signalling components IL-1R1 and IL-1R accessory protein (AcP) are dispensable for expulsion of this parasite. IL-1 is thus critical for CD4(+) Th2-mediated immunity to T. muris; however, this action is independent of the established IL-1 signalling receptor. We also present data demonstrating that both IL-1alpha and IL-1beta induce measurable effects on T. muris primed cells isolated from IL-1R1 or IL-1R AcP null mice. MLN cells from these mice restimulated with parasite antigen proliferated at a greater rate and produced more cytokines in response to exogenous IL-1. This ability to respond to IL-1 was restricted to these parasite-primed cells and importantly was not evident in cells from naïve gene null mice. These in vitro data are consistent with the observed ability of mice with compromised IL-1 signalling to expel the parasite, bolstering the premise that an alternative IL-1 signalling mechanism is accessible in the context of an intestinal helminth-driven Th2 immune response.
Humphreys
Neil E
NE
Faculty of Life Sciences, The University of Manchester, Manchester, UK. Neil.e.humphreys@manchester.ac.uk
Grencis
Richard K
RK
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000276:immunology / Q000469:parasitology*; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology / Q000469:parasitology; D014257:Trichuriasis / Q000276:immunology*; D014258:Trichuris / Q000276:immunology*
D000947:Antigens, Helminth; D016207:Cytokines; C507767:Il1rap protein, mouse; D053577:Interleukin-1 Receptor Accessory Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I