Abstract
The glucocorticoid-induced TNFR-related (GITR) protein is a member of the tumor necrosis factor receptor superfamily influencing natural and acquired immune response. GITR is activated by its ligand, GITRL, mainly expressed on antigen presenting cells. Previously, we demonstrated that GITR plays a role in regulating immune response to Candida albicans. Here we analyzed whether GITRL-GITR interaction influences the recognition of C. albicans by regulating the expression of pattern recognition receptors on splenic dendritic cells. Our report demonstrates that under physiological conditions and during candidiasis the GITRL-GITR system affects TLR-2 and TLR-4 expression on DC. These changes correlate with decrease in: MyD88 activation; CD80 and CD40 expression on DC; T cell activation response, including CD28 expression, IL-2 and IFN-gamma production. Our results point out that, during fungal infection, GITRL-GITR interaction modulates TLR-4 and TLR-2 expression, thereby altering the antigen presentation process, and suggesting a role of GITRL-GITR interaction in resistance against infectious diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B7-1 Antigen / immunology
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B7-1 Antigen / metabolism
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CD28 Antigens / immunology
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CD28 Antigens / metabolism
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / microbiology
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CD40 Antigens / immunology
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CD40 Antigens / metabolism
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Candida albicans / immunology
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Candidiasis / immunology*
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Candidiasis / microbiology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / microbiology
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Glucocorticoid-Induced TNFR-Related Protein
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Interferon-gamma / biosynthesis
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Interferon-gamma / immunology
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Interleukin-2 / biosynthesis
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Interleukin-2 / immunology
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Mice
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Mice, Knockout
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Myeloid Differentiation Factor 88 / immunology
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Myeloid Differentiation Factor 88 / metabolism
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / immunology
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Receptors, Nerve Growth Factor / metabolism*
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / immunology
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Receptors, Tumor Necrosis Factor / metabolism*
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Toll-Like Receptor 2 / immunology
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Toll-Like Receptor 2 / metabolism
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Toll-Like Receptor 4 / immunology
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Toll-Like Receptor 4 / metabolism
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Tumor Necrosis Factors / immunology
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Tumor Necrosis Factors / metabolism*
Substances
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B7-1 Antigen
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CD28 Antigens
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CD40 Antigens
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Glucocorticoid-Induced TNFR-Related Protein
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Interleukin-2
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Receptors, Nerve Growth Factor
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Receptors, Tumor Necrosis Factor
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Tlr2 protein, mouse
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Tlr4 protein, mouse
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Tnfrsf18 protein, mouse
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Tnfsf18 protein, mouse
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Tumor Necrosis Factors
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Interferon-gamma