Abstract
To decipher early promoters of the local microenvironment for Th2-type immunity, we wanted to identify gene patterns that were induced by Leishmania major in the infected skin of susceptible, Th2-prone BALB/c, but not of resistant, Th1-prone C57BL/6 mice. We found a marked up-regulation of the chemokine I-TAC (Cxcl11) during the first 2 d of infection in the epidermis of susceptible but not of resistant mice. Accordingly, local injection of I-TAC (2×1 μg) in resistant mice on the first day of infection resulted in a Th2-driven, sustained deterioration of disease and dramatically enhanced parasite levels. On the cellular level, I-TAC decreased IL-12 production by dendritic cells (DCs) in skin-draining lymph nodes and by DCs in vitro. Thus, we demonstrate for the first time that epidermis-derived I-TAC triggers a sustained Th2-response that determines the outcome of a complex immunological process.
Keywords:
keratinocytes; leishmaniasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptive Immunity / genetics
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Adaptive Immunity / immunology*
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Animals
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Chemokine CXCL11 / genetics
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Chemokine CXCL11 / immunology*
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Chemokine CXCL11 / metabolism
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Epidermis / immunology*
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Epidermis / metabolism
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Epidermis / parasitology
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Fluorescent Antibody Technique
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Gene Expression / immunology
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Host-Parasite Interactions / immunology
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In Situ Hybridization
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Interleukin-12 / genetics
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Interleukin-12 / immunology
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Interleukin-12 / metabolism
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Leishmania major / immunology
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Leishmania major / physiology
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Leishmaniasis, Cutaneous / genetics
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Leishmaniasis, Cutaneous / immunology
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Leishmaniasis, Cutaneous / parasitology
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Reverse Transcriptase Polymerase Chain Reaction
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Skin / immunology
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Skin / metabolism
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Skin / parasitology
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Th2 Cells / immunology*
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Th2 Cells / metabolism
Substances
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Chemokine CXCL11
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Interleukin-12