Neither interleukin-4 receptor alpha expression on CD4+ T cells, or macrophages and neutrophils is required for protective immunity to Trichinella spiralis.

ABSTRACT

The T helper type 2 (Th2) mediated expulsion of the gastrointestinal nematode Trichinella spiralis requires interleukin-4 receptor alpha (IL-4Ralpha) expression on both bone-marrow-derived and non-bone-marrow-derived cells. To more definitively investigate the role of IL-4/IL-13 responsiveness in the development of protective immunity to T. spiralis, cell-specific IL-4Ralpha signalling on CD4(+) T cells (Lck(cre) IL-4Ralpha(-/flox)) and macrophages/neutrophils (LysM(cre) IL-4Ralpha(-/flox)) was analysed on the BALB/c background. Infection of wild-type and control IL-4Ralpha(-/flox) mice induced a Th2-type immune response with elevated IL-4 cytokine production, parasite-specific immunoglobulin G1 (IgG1), total IgE, intestinal mastocytosis and enteropathy. In contrast, global IL-4Ralpha-deficient BALB/c mice showed reduced worm expulsion, antibody production, intestinal mastocytosis and gut pathology. BALB/c mice generated with cell-specific deletion of IL-4Ralpha on CD4(+) T lymphocytes or macrophages/neutrophils, controlled gastrointestinal helminth infection by eliciting a protective immune response comparable to that observed with wild-type and IL-4Ralpha(-/flox) controls. Together, this shows that the development of host protective Th2 responses accompanied by parasite loss is independent of IL-4Ralpha expression on CD4(+) T cells and macrophages/neutrophils.