Abstract
c-Jun N-terminal kinase (JNK) is a mitogen-activated protein kinase that plays important regulatory roles in helper T cell differentiation. In the current study, we used Jnk1-deficient mice to examine the function of JNK during an in vivo pathogenic infection, leishmaniasis, which is strongly influenced by Th1/Th2 effector mechanisms. The data show that Jnk1-deficient mice, despite their usually genetically resistant background, were unable to resolve Leishmania infections. Jnk1-/- mice displayed reduced delayed-type hypersensitivity in response to the pathogen, which was associated with a T cell defect. We found that, although these mice can direct an apparent Th1-response, there is also simultaneous generation of Leishmania-specific Th2 responses, which possibly down-modulate protective Th1-mediated immune function. These findings demonstrate that the negative regulation of Th2 cytokine production by the JNK1 signaling pathway is essential for generating Th1-polarized immunity against intracellular pathogens, such as Leishmania major.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / enzymology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / parasitology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cytokines / biosynthesis
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Cytokines / physiology
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Hypersensitivity, Delayed / genetics
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Hypersensitivity, Delayed / immunology
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Hypersensitivity, Delayed / parasitology
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Immunity, Cellular / genetics
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Leishmania major / immunology*
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Leishmaniasis, Cutaneous / enzymology*
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Leishmaniasis, Cutaneous / genetics
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Leishmaniasis, Cutaneous / immunology*
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Lymphocyte Activation / genetics
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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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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases / deficiency
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / physiology*
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / enzymology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / parasitology
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Th1 Cells / cytology
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Th1 Cells / enzymology
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Th1 Cells / immunology
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Th1 Cells / parasitology
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Th2 Cells / cytology
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Th2 Cells / enzymology
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Th2 Cells / immunology
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Th2 Cells / parasitology
Substances
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Cytokines
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases