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Infection and Immunity, December 2005, p. 7853-7859, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.7853-7859.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Decreased In Situ Expression of Interleukin-10 Receptor Is Correlated with the Exacerbated Inflammatory and Cytotoxic Responses Observed in Mucosal Leishmaniasis

Department of Morphology,¹ Department of Biochemistry-Immunology,² Department of Pharmacology, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte,⁴ Health Sciences School, Educational Community Foundation of Formiga, Formiga, Minas Gerais,³ Immunology Service, HUPES, Federal University of Bahia, Salvador, Bahia, Brazil⁵

Received 1 June 2005/ Returned for modification 11 July 2005/ Accepted 20 August 2005

Human infection with Leishmania braziliensis can lead to cutaneous leishmaniasis (CL) or mucosal leishmaniasis (ML). We hypothesize that the intense tissue destruction observed in ML is a consequence of an uncontrolled exacerbated inflammatory immune response, with cytotoxic activity. For the first time, this work identifies the cellular sources of inflammatory and antiinflammatory cytokines, the expression of effector molecules, and the expression of interleukin-10 (IL-10) receptor in ML and CL lesions by using confocal microscopy. ML lesions displayed a higher number of gamma interferon (IFN-)-producing cells than did CL lesions. In both ML and CL, CD4⁺ cells represented the majority of IFN--producing cells, followed by CD8⁺ cells and CD4^– CD8^– cells. The numbers of tumor necrosis factor alpha-positive cells, as well as those of IL-10-producing cells, were similar in ML and CL lesions. The effector molecule granzyme A showed greater expression in ML than in CL lesions, while inducible nitric oxide synthase did not. Finally, the expression of IL-10 receptor was lower in ML than in CL lesions. Thus, our data identified distinct cytokine and cell population profiles for CL versus ML patients and provide a possible mechanism for the development of ML disease through the demonstration that low expression of IL-10 receptor is present in conjunction with a cytotoxic and inflammatory profile in ML.

Editor: W. A. Petri, Jr.

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