Neither interleukin-4 receptor alpha expression on CD4+ T cells, or macrophages and neutrophils is required for protective immunity to Trichinella spiralis.
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.
Michels
Chesney E
CE
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
Scales
Hannah E
HE
Saunders
Karin A
KA
McGowan
S
S
Brombracher
Frank
F
Alexander
James
J
Lawrence
Catherine E
CE
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007421:Intestine, Small / Q000276:immunology / Q000469:parasitology; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000469:parasitology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology*; D053662:Interleukin-4 Receptor alpha Subunit
D007073:Immunoglobulin E; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit