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Published online before print June 18, 2008

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0308211

Received for publication March 27, 2008.
Revised May 15, 2008.
Accepted for publication May 22, 2008.

Article

Fonsecaea pedrosoi infection induces differential modulation of costimulatory molecules and cytokines in monocytes from patients with severe and mild forms of chromoblastomycosis

Maria Glória Teixeira Sousa ^*, Conceição de Maria Pedrozo e Silva Azevedo , Rosana Cicera Nascimento ^*, Eliver Eid Bou Ghosn ^*, Karla Leticia Santiago ^*, Vanessa Noal ^*, Gisele Facholi Bomfim ^*, Sirlei Garcia Marques , Azizedite Guedes Gonçalves , Daniel Wagner de Castro Lima Santos , and Sandro Rogerio Almeida ^*@

Departamento de Patologia, Universidade Federal do Maranhão, São Luís/Maranhão, Brazil; and *Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Brazil

^@ To whom correspondence should be addressed. E-mail: sandroal{at}usp.br.

	Abstract

The host defense mechanism in chromoblastomycosis has not been thoroughly investigated. It has been suggested that cell-mediated immunity in patients with long-standing chromoblastomycosis is somehow impaired. As a result, these individuals became unable to develop an efficient immune reaction. Many studies have shown that monocyte-derived macrophages exhibit critical activities in immunity to microorganisms. Moreover, the ability of cells from the monocytic lineage to process and present antigens, to produce cytokines, and to provide costimulatory signals confirms their pivotal role in the initiation of specific immune responses. In the present study, it was observed that monocytes from patients with a severe form of disease had a higher production of IL-10 and a lower expression of HLA-DR and costimulatory molecules when stimulated with specific antigen or LPS. Immune modulation with recombinant IL-12 or anti-IL-10 can restore the antigen-specific Th1-type immune response in chromoblastomycosis patients by up-regulating HLA-DR and costimulatory molecules in monocytes. Therefore, our data show that monocytes from patients with different clinical forms of chromoblastomycosis present distinct phenotypic and functional profiles. This observation suggests possible mechanisms that control the T cell response and influence their role in the development of pathology.

Key Words: immune regulation • Th1/Th2 • IL-12 • IL-10