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Published online before print September 21, 2007

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(Journal of Leukocyte Biology. 2007;82:1401-1406.)
© 2007 by Society for Leukocyte Biology

Leishmania amazonensis infection impairs differentiation and function of human dendritic cells

Cecilia Favali^*,, Natália Tavares^*, Jorge Clarêncio^*, Aldina Barral^*,,, Manoel Barral-Netto^*,, and Claudia Brodskyn^*,,1

^* Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil; and
Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia, Brazil;
PPGIm, Instituto de Ciências da Saúde da Universidade Federal da Bahia, Salvador, Bahia, Brazil; and
Instituto de Investigação em Imunologia (iii), São Paulo, Brazil

¹Correspondence: Laboratório de Imunoparasitologia, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua Waldemar Falcão, 121, Candeal, Salvador Bahia, Brazil. E-mail: brodskyn{at}bahia.fiocruz.br

ABSTRACT

Dendritic cells (DCs) are of utmost importance in initiating an immune response and may also function as targets for pathogens. The presence of pathogens inside DCs is likely to impair their functions and thus, influence immune responses. In the present report, we evaluated the impact of the presence of Leishmania amazonensis during differentiation and maturation of human monocyte-derived DCs. The presence of live L. amazonensis parasites during DC differentiation led to a significant decrease in CD80 (92%) and CD1a (56%) expression and an increase in CD86 (56%) cell surface expression. Phenotypic changes were accompanied by a lower secretion of IL-6, observed after 6 days of DC differentiation in the presence of L. amazonensis. DCs differentiated in the presence of L. amazonensis were used as APC in an autologous coculture, and lower amounts of IFN- were obtained compared with control DCs differentiated in the absence of parasites. The effect of heat-killed parasites, but not of Leishmania antigen, during DC differentiation and maturation was similar to that observed with viable parasites. During maturation, the presence of live L. amazonensis parasites, but not of soluble Leishmania antigen, led to a decrease in IL-6 and IL-10 production. In this way, we observed that the parasite is able to abrogate full DC differentiation, causing a delay in the immune response and likely, favoring its establishment in human hosts.

Key Words: Leishmaniasis • antigen-presenting cells • cytokines • costimulatory molecules • T cells

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