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Infect. Immun. doi:10.1128/IAI.00499-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Role of IL-1 in Activating CD11c^highCD45RB^- DC Subset and Priming Leishmania amazonensis-specific CD4⁺ T cells in vitro and in vivo

Department of Microbiology and Immunology, Department of 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, TX, USA, Department of Infectious Diseases, Harbin Medical University, Hei Long Jiang Province, China

^* To whom correspondence should be addressed. Email: lysoong{at}utmb.edu.

	Abstract

Cutaneous leishmaniasis associated with Leishmania amazonensis (La) infection is characterized by uncontrolled parasite replication and profound immunosuppression; however, the underlying mechanisms remain largely unclear. One possibility is that La parasite modulates antigen-presenting cells, favoring the generation of pathogenic Th cells that are capable of recruiting leukocytes, but insufficient to fully activate their microbicidal activities. To test this possibility, we infected marrow-derived DCs of C57BL/6 mice with La or L. major promastigotes and assessed the activation of DC subsets and their capacity in priming CD4⁺ T cells in vitro. In comparison to L. major controls, La-infected DCs secreted lower levels of IL-1 and IL-1, were less potent in activating IL-12p40-producing CD11c^highCD45RB^-CD83⁺CD40⁺ DC subset, and preferentially activated CD4⁺ T cells with an IFN-^lowIL-10^highIL-17^high phenotype. Although the addition of IL-1 at the time of infection markedly enhanced DC activation and T cell priming, it did not skew the cytokine profile of DCs and pathogenic Th cells, as local injection of IL-1 following La infection accelerated Th cell activation and disease progression. This study suggests that intrinsic defects at the level of DC activation are responsible for susceptible phenotype in La-infected hosts, and that this parasite may have evolved unique mechanisms to interfere with innate and adaptive immunity.

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