Effects of CXCL10 on Dendritic Cell and CD4+T-Cell Functions duringLeishmania amazonensisInfection
Copyright policy )Effects of CXCL10 on Dendritic Cell and CD4+T-Cell Functions duringLeishmania amazonensisInfection
ABSTRACTLeishmania amazonensiscan cause progressive disease in most inbred strains of mice. We have previously reported that treatment with CXCL10 activates macrophage (MΦ) effector function(s) in parasite killing and significantly delays lesion development in susceptible C57BL/6 mice via enhanced gamma interferon (IFN-γ) and interleukin 12 (IL-12) secretion; however, the mechanism underlying this enhanced immunity againstL. amazonensisinfection remains largely unresolved. In this study, we utilized stationary promastigotes to infect bone marrow-derived dendritic cells (DCs) of C57BL/6 mice and assessed the activation of DC subsets and the capacity of these DC subsets to prime CD4+T cells in vitro. We found that CXCL10 induced IL-12 p40 production but reduced IL-10 production in uninfected DCs. YetL. amazonensis-infected DCs produced elevated levels of IL-10 despite CXCL10 treatment. Elimination of endogenous IL-10 led to increased IL-12 p40 production in DCs as well as increased proliferation and IFN-γ production by in vitro-primed CD4+T cells. In addition, CXCL10-treated CD4+T cells became more responsive to IL-12 via increased expression of the IL-12 receptor β2chain and produced elevated levels of IFN-γ. This report indicates the utility of CXCL10 in generating a Th1-favored, proinflammatory response, which is a prerequisite for controllingLeishmaniainfection.
- The University of Texas System United States
- The University of Texas Medical Branch at Galveston United States
CD4-Positive T-Lymphocytes, Leishmania, Interleukin-12 Subunit p40, Receptors, Interleukin-12, Dendritic Cells, Interleukin-10, Chemokine CXCL10, Mice, Inbred C57BL, Interferon-gamma, Mice, Protein Subunits, Gene Expression Regulation, Animals, Leishmaniasis, Cells, Cultured, Gene Deletion
CD4-Positive T-Lymphocytes, Leishmania, Interleukin-12 Subunit p40, Receptors, Interleukin-12, Dendritic Cells, Interleukin-10, Chemokine CXCL10, Mice, Inbred C57BL, Interferon-gamma, Mice, Protein Subunits, Gene Expression Regulation, Animals, Leishmaniasis, Cells, Cultured, Gene Deletion
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