IAI Accepts, published online ahead of print on 9 November 2009

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Infect. Immun. doi:10.1128/IAI.00959-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

CXCL10 production by human monocytes in response to Leishmania braziliensis infection

Diego A. Vargas-Inchaustegui, Alison E. Hogg, Gianfranco Tulliano, Alejandro Llanos-Cuentas, Jorge Arevalo, Janice J. Endsley, and Lynn Soong^*

Department of Microbiology and Immunology, Department of Pathology, Institute for Human Infections and Immunity, Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX 77555; Instituto de Medicina Tropical "Alexander von Humboldt", Universidad Peruana Cayetano Heredia, Lima, Peru

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

Leishmania (Viannia) braziliensis is the causative agent of mucocutaneous leishmaniasis (ML) in South America, and ML is characterized by excessive T and B cell responses to the parasite. We speculate that the unbalanced production of inflammatory mediators in response to L. braziliensis infection contributes to cell recruitment and disease severity. To test this hypothesis, we first examined the response of healthy volunteer peripheral blood mononuclear cells (PBMCs) to L. braziliensis infection. We observed that while L. braziliensis infection induced the production of CXCL10 and IL-10 in human PBMCs and macrophages (Ms), an enhanced expression of CXCL10 and its receptor CXCR3 was predominantly detected in CD14⁺ monocytes. The chemoattractant factors secreted by L. braziliensis-infected cells were highly efficient in recruiting un-infected PBMCs (predominantly CD14⁺ cells) through transwell membranes. Sera of American tegumentary leishmaniasis (ATL) patients (especially the ML cases) had significantly higher levels of CXCL10, CCL4 and soluble TNF receptor II (sTNFRII) than did those of control subjects. Our results suggest that, following L. braziliensis infection, the production of multiple inflammatory mediators by the host may contribute to disease severity by increasing cellular recruitment.