High levels of susceptibility and T helper 2 response in MyD88-deficient mice infected with Leishmania major are interleukin-4 dependent.
Myeloid differentiation protein 88 (MyD88) is a general adaptor for the signaling cascade through receptors of the Toll/IL-1R family. When infected with Leishmania major parasites, MyD88-deficient mice displayed a dramatically enhanced parasite burden in their tissues similar to that found in susceptible BALB/c mice. In contrast, MyD88 knockout mice did not develop ulcerating lesions despite a lack of interleukin-12 (IL-12) production and a predominant T helper 2 cell response. Blockade of IL-4 produced early (day 1) after infection restored a protective T helper 1 response in MyD88 knockout mice.
Debus
Andrea
A
Institut für Klinische Mikrobiologie, Immunologie und Hygiene der Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
Gläsner
Joachim
J
Röllinghoff
Martin
M
Gessner
André
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D004198:Disease Susceptibility; D005260:Female; D015847:Interleukin-4 / Q000378:metabolism*; D018320:Leishmania major / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D000913:Antibodies, Protozoan; D000943:Antigens, Differentiation; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; D015847:Interleukin-4