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Modulation of Dendritic Cell Function by Leishmania Parasites¹

Departments of Microbiology & Immunology and 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 77555

The interactions between Leishmania parasites and dendritic cells (DCs) are complex and involve paradoxical functions that can stimulate or halt T cell responses, leading to the control of infection or progression of disease. The magnitude and profile of DC activation vary greatly, depending upon the Leishmania species/strains, developmental stages, DC subsets, serum opsonization, and exogenous DC stimuli involved in the study. In general, the uptake of Leishmania parasites alone can trigger relatively weak and transient DC activation; however, the intracellular parasites (amastigotes) are capable of down-modulating LPS/IFN--stimulated DC activation via multiple mechanisms. This review will highlight current data regarding the initial interaction of DC subsets with invading parasites, the alterations of DC signaling pathways and function by amastigotes, and the impact of DC functions on protective immunity and disease pathogenesis. Available information provides insight into the mechanisms by which DCs discriminate between the types of pathogens and regulate appropriate immune responses.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI043003 and AI039540).

² Address correspondence and reprint requests to Dr. Lynn Soong, Department of Microbiology and Immunology, University of Texas Medical Branch, Medical Research Building 3.142, 301 University Boulevard, Galveston, TX 77555-1070. E-mail address: lysoong{at}utmb.edu

³ Abbreviations used in this paper: M, macrophage; DC, dendritic cell; DC-SIGN, dendritic cell-specific ICAM-3-grabbing nonintegrin; LC, Langerhans cell; LN, lymph node; LPG, lipophosphoglycan; mDC, myeloid DC; pDC, plasmacytoid DC; PMN, polymorphonuclear neutrophil.

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