Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Antibodies, Protozoan / blood
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Antigens, Differentiation / genetics
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Antigens, Differentiation / metabolism
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Disease Susceptibility
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Female
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Interleukin-4 / metabolism*
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Leishmania major / immunology
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Leishmania major / isolation & purification
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Leishmania major / pathogenicity*
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Leishmaniasis, Cutaneous / immunology*
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Leishmaniasis, Cutaneous / parasitology
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Leishmaniasis, Cutaneous / physiopathology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Myeloid Differentiation Factor 88
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Receptors, Immunologic / deficiency*
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism
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Th1 Cells / immunology
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Th2 Cells / immunology*
Substances
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Adaptor Proteins, Signal Transducing
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Antibodies, Protozoan
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Antigens, Differentiation
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Receptors, Immunologic
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Interleukin-4