Immunological and genetic evidence for a crucial role of IL-10 in cutaneous lesions in humans infected with Leishmania braziliensis.
In populations exposed to Leishmania braziliensis, certain subjects develop skin ulcers, whereas others are naturally protected against cutaneous leishmaniasis. We have evaluated which cytokines are most crucial in the development of skin lesions. We found that active lesions occur in subjects with polarized Th2 or mixed Th1/Th2 responses, both associated with elevated IL-10 production. IL-10 was strongly associated (p = 0.004, odd ratio (OR) = 6.8, confidence interval = 1.9-25) with lesions, excluding IFN-gamma, IL-12, TNF, IL-13, and IL-4 from the regression model. IL-10 was produced by blood monocytes and CD4(+)CD25(+) T lymphocytes (mostly Foxp3(+)). However, we did not observe any difference between the number of these cells present in the blood of subjects with active lesions and those present in resistant subjects. Genetic analysis of the IL10-819C/T polymorphism, located in the IL10 promoter, showed that the C allele increased the risk of lesions (OR = 2.5 (1.12-5.7), p = 0.003). Functional analysis of these variants showed allele-specific binding of nuclear factors. The IL10-819C/C genotype was associated with higher levels of IL-10 than C/T and T/T genotypes. These observations demonstrate an important role for IL-10 in skin lesions in humans infected with L. braziliensis, and identify circulating monocytes and Tregs as principal sources of IL-10 in these patients.
Salhi
Adnene
A
Institut National de la Santé et de la Recherche Médicale U399, Faculty of Medicine, 17 Boulevard Jean Moulin, Marseille cedex 05, France.
Rodrigues
Virmondes
V
Santoro
Ferrucio
F
Dessein
Helia
H
Romano
Audrey
A
Castellano
Lucio Roberto
LR
Sertorio
Mathieu
M
Rafati
Sima
S
Chevillard
Christophe
C
Prata
Aluisio
A
Alcaïs
Alexandre
A
Argiro
Laurent
L
Dessein
Alain
A
D000328:Adult; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology*; D007892:Leishmania braziliensis / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; C508609:IL10 protein, human; D016753:Interleukin-10