Expression of SmATPDase 1 and SmATPDase 2 in Schistosoma mansoni eggs favors IL-10 mediated immune system modulation in infected individuals.

Thalisson Artur Ribeiro Gomides, Márcio Luís Moreira Souza,Amanda Braga Figueiredo, Marlucy Rodrigues Lima, Alda Maria Soares Silveira, Girley Francisco Machado Assis,Lucia Alves de Oliveira Fraga, Gabriela Silveira-Nunes, Leticia Martucci, Jennifer Delgado Garcia, Luís Carlos Crocco Afonso,Andréa Teixeira-Carvalho,Pauline Martins Leite

crossref(2023)

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摘要
Abstract Background Schistosomiasis is a chronic disease that affects over 200 million people worldwide. A pivotal role of IL-10 is down-regulating Th1 and Th2 responses to schistosome antigens, which can favor the parasite establishment. The SmATPDases degrade ATP and ADP in AMP and adenosine, a molecule with anti-inflammatory properties. We evaluated the expression of SmATPDases 1 and 2 enzymes in S. mansoni eggs obtained from infected individuals as a possible parasite-related factor that could influence the host immune response and the clinical outcome of the disease. Methods Fecal samples were collected from 40 infected individuals to detect coding regions of the enzymes by the qPCR. The production of cytokines was measured in supernatants of PBMC cultures. The analysis was performed by the global median determination for each cytokine and set up high producers (HP) of cytokines. Results Six individuals expressed SmATPDase 1 in their fecal samples, 6 expressed SmATPDase 2, and 6 expressed both enzymes. The group who expressed only SmATPDase 1 showed a high frequency of IFN-γ, TNF, IL-4 HP, and a low frequency of IL-6 HP. The group who expressed only SmATPDase 2 showed a high frequency of IFN-γ, IL-6, and IL-4 HP and a low frequency of IL-10 HP. The group who expressed both enzymes showed a high frequency of IL-10 HP and low frequencies of IFN-γ, IL-6, IL-2, IL-4, and IL-13 HP. In the group that had SmATPDase 2 expression was observed higher indices the ratio between IFN-γ/IL-10 than individuals that showed expression both enzymes. The positive correlation between infection intensity and IL-10 levels remained only in the positive SmATPDase group. Overall, the analysis revealed that 62.5% of the cytokines presented reduced frequency in the group of individuals expressing both enzymes, the IL-10 is the only cytokine induced by the expression of both enzymes and the expression profile of SmATPDases is relevant data for grouping individuals. Conclusions The expression of both enzymes in the parasite's eggs seems to be a new undescribed factor that negatively modulates the host immune response by inducing high IL-10 production, which, in turn, can contribute to the survival of the parasite.
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