CD4(+) CD25(+) Foxp3(+) Regulatory T Cells, Dendritic Cells, and Circulating Cytokines in Uncomplicated Malaria: Do Different Parasite Species Elicit Similar Host Responses?

Autor(es)

Goncalves, Raquel M. ^[1] ; Salmazi, Karina C. ^[2] ; Santos, Bianca A. N. ^[2] ; Bastos, Melissa S. ^[1] ; Rocha, Sandra C. ^[1] ; Boscardin, Silvia B. ^[1] ; Silber, Ariel M. ^[1] ; Kallas, Esper G. ^[2] ; Ferreira, Marcelo U. ^[1] ; Scopel, Kezia K. G. ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Parasitol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Div Clin Immunol & Allergy, BR-05508900 Sao Paulo - Brazil

^[3] Univ Fed Juiz de Fora, Inst Biol Sci, Juiz De Fora - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Infection and Immunity; v. 78, n. 11, p. 4763-4772, NOV 2010.
• Citações Web of Science: 50

Resumo

Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. Here we show that during uncomplicated acute malaria, both species induced a significant expansion of CD4(+) CD25(+) Foxp3(+) Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123(+)), with a decrease in the myeloid/plasmacytoid DC ratio. These changes were proportional to parasite loads but correlated neither with the intensity of clinical symptoms nor with circulating cytokine levels. One-third of P. vivax-infected patients, but no P. falciparum-infected subjects, showed impaired maturation of circulating DCs, with low surface expression of CD86. Although vivax malaria patients overall had a less inflammatory cytokine response, with a higher interleukin-10 (IL-10)/tumor necrosis factor alpha (TNF-alpha) ratio, this finding did not translate to milder clinical manifestations than those of falciparum malaria patients. We discuss the potential implications of these findings for species-specific pathogenesis and longlasting protective immunity to malaria. (AU)

• Processo FAPESP: 07/52771-0 - Regulacao da resposta imune celular na malaria humana: o papel das celulas t-reg cd4+cd25+.
• Beneficiário: Marcelo Urbano Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/50645-0 - Interação entre células T reguladoras CD4+CD25+Foxp3+ e células dendríticas na regulação da resposta imune celular contra Plasmodium falciparum
• Beneficiário: Marcelo Urbano Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular