Effects of CXCL10 on dendritic cell and CD4+ T-cell functions during Leishmania amazonensis infection.
Leishmania amazonensis can cause progressive disease in most inbred strains of mice. We have previously reported that treatment with CXCL10 activates macrophage (MPhi) effector function(s) in parasite killing and significantly delays lesion development in susceptible C57BL/6 mice via enhanced gamma interferon (IFN-gamma) and interleukin 12 (IL-12) secretion; however, the mechanism underlying this enhanced immunity against L. amazonensis infection 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. Yet L. 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-gamma 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 beta2 chain and produced elevated levels of IFN-gamma. This report indicates the utility of CXCL10 in generating a Th1-favored, proinflammatory response, which is a prerequisite for controlling Leishmania infection.
Vasquez
René E
RE
Department of Microbiology and Immunology, Center for Biodefense and Emerging Infectious Diseases, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070, USA.
Xin
Lijun
L
Soong
Lynn
L
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000494:pharmacology* / Q000627:therapeutic use; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000378:metabolism; D007891:Leishmania / Q000145:classification / Q000502:physiology*; D007896:Leishmaniasis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D021122:Protein Subunits; D053707:Receptors, Interleukin-12 / Q000378:metabolism
D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D053707:Receptors, Interleukin-12; D016753:Interleukin-10; D007371:Interferon-gamma