Infection of IL-4-deficient mice with the parasitic nematode Brugia malayi demonstrates that host resistance is not dependent on a T helper 2-dominated immune response.
Resistance of intact mice to infection with the filarial nematode, Brugia malayi is dependent on the presence of T cells. To investigate the role of Th2 cells in this protection, mice with a targeted disruption of the IL-4 gene were infected with different developmental stages of B. malayi. We examined the phenotypic changes in the immune response and the survival of each stage in these mice. In wild-type mice, adult female worms induce Th2 responses, characterized by antigen-specific IgG1 production, elevated IgE, and marked IL-4 secretion by splenocytes stimulated in vitro with Brugia extract. However, first stage larvae (microfilariae), induce Th1 responses with the appearance of antigen-specific IgG2a, IgG2b, and IgG3 and IFN-gamma secretion by splenocytes. Infection of IL-4-deficient mice revealed a dramatic change in the response to adult worms, with a severe reduction in IgG1 production and a corresponding increase in the production of IgG2a, IgG2b, IgG3, and IFN-gamma release. The switch to Th1-type responses was particularly marked in IL-4-deficient recipients of female worms, which continually release live microfilariae. In the absence of IL-4, down-regulation of the microfilarial-induced Th1 response does not occur. Despite these profound alterations to the immune response in IL-4-deficient mice, survival of infective larvae, adult worms, or microfilariae in the peritoneal cavity was unaffected. In mice, therefore, the prominent Th2-type response elicited by filarial parasites may not be an essential component of the host protective immune response.
Lawrence
R A
RA
Wellcome Research Centre for Parasitic Infections, Department of Biology, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Allen
J E
JE
Gregory
W F
WF
Kopf
M
M
Maizels
R M
RM
D000818:Animals; D017178:Brugia malayi / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005368:Filariasis / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D007136:Immunoglobulins / Q000145:classification; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000032:analysis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D007136:Immunoglobulins; D008222:Lymphokines; D015847:Interleukin-4