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Infection and Immunity, January 2008, p. 161-169, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.00825-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Effects of CXCL10 on Dendritic Cell and CD4⁺ T-Cell Functions during Leishmania amazonensis Infection

Departments of Microbiology and Immunology,¹ Pathology, Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas 77555-1070²

Received 15 June 2007/ Returned for modification 23 July 2007/ Accepted 27 October 2007

Leishmania amazonensis can cause progressive disease in most inbred strains of mice. We have previously reported that treatment with CXCL10 activates macrophage (M) effector function(s) in parasite killing and significantly delays lesion development in susceptible C57BL/6 mice via enhanced gamma interferon (IFN-) 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- 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 β₂ chain and produced elevated levels of IFN-. This report indicates the utility of CXCL10 in generating a Th1-favored, proinflammatory response, which is a prerequisite for controlling Leishmania infection.

Published ahead of print on 12 November 2007.

Editor: J. F. Urban, Jr.