Up-regulation of Th1-type responses in mucosal leishmaniasis patients.
The cytokine profile produced by peripheral blood mononuclear cells (PBMC) in response to leishmania antigens and the ability of interleukin-10 (IL-10) and transforming growth factor beta (TGF-beta) to modulate the immune response were evaluated in 21 mucosal leishmaniasis patients. Patients with mucosal disease exhibited increased gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) secretion and decreased IL-10 secretion compared to patients with classical cutaneous leishmaniasis. CD4(+) Th1 cells were the main source of IFN-gamma and TNF-alpha production in mucosal leishmaniasis patients. Evaluation of cytokine gene expression in PBMC of these patients showed that there was strong up-regulation of IFN-gamma transcripts upon stimulation with leishmania antigen, in contrast to the baseline levels of IL-10 mRNA. IL-10 suppressed IFN-gamma production by 48% in cell cultures from cutaneous leishmaniasis patients and by 86% in cell cultures from healthy subjects stimulated with purified protein derivative, whereas in similar conditions IL-10 suppressed IFN-gamma production by 19% in cell cultures from mucosal leishmaniasis patients stimulated with leishmania antigen. TGF-beta suppressed IFN-gamma levels to a greater extent in healthy subjects than in mucosal leishmaniasis and cutaneous leishmaniasis patients. These data indicate that a poorly modulated T-cell response in mucosal leishmaniasis patients leads to production of high levels of proinflammatory cytokines, such as IFN-gamma and TNF-alpha, as well as a decreased ability of IL-10 and TGF-beta to modulate this response. These abnormalities may be the basis for the pathological findings observed in this disease.
Bacellar
Olívia
O
Serviço de Imunologia do Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.
Lessa
Hélio
H
Schriefer
Albert
A
Machado
Paulo
P
Ribeiro de Jesus
Amélia
A
Dutra
Walderez O
WO
Gollob
Kenneth J
KJ
Carvalho
Edgar M
EM
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000378:metabolism; D007891:Leishmania / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology; D007897:Leishmaniasis, Mucocutaneous / Q000276:immunology* / Q000503:physiopathology; D018417:Th1 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma