Dados do Trabalho

Título

New insights into schistosomiasis mansoni pathogenesis: evidence for bacterial translocation, inflammasome activation, and upregulation of proinflammatory cytokines in hepatosplenic patients

Introdução

IL13 drives schistosomiasis fibrogenesis, but growing evidence suggests that IL1beta and IL17 contribute to severe disease.

Objetivo (s)

Our aims were to evaluate the immune response in patients with schistosomiasis and determine if liver fibrosis is associated with bacterial translocation, inflammasome activation, and Th17 response.

Material e Métodos

Plasma samples from non-infected individuals (n=30) and from patients with acute (n=22), hepatointestinal (n=40), and hepatosplenic (n=26) schistosomiasis mansoni were collected. ELISA was performed for IL1beta, IL5, IL6, IL10, IL13, IL17, TNFalpha, IFNgamma, CCL11, and CCL17. Snap-frozen liver biopsies from non-infected individuals (n=6) and hepatosplenic patients (n=36) were also included. Real-time PCR was performed for genes related to bacterial translocation, inflammasome activation, immune response, and fibrogenesis. Liver fibrosis was assessed by ultrasound (WHO protocol).

Resultados e Conclusão

Patients with acute schistosomiasis had higher levels of IL1beta, IL5, IL6, IL10, IL13, IL17, TNFalpha, CCL11, and CCL17 than hepatointestinal patients or non-infected controls. Hepatosplenic patients had higher IL13, IL5, IL1beta, TNFalpha, and CCL11, but lower CCL17 levels than hepatointestinal patients or non-infected individuals. IL-5, IL-13, IL-1beta, TNFalpha, and CCL11 positively correlated with the degree of fibrosis, while CCL17 levels were negatively correlated. Hepatosplenic patients had increased liver expression of markers of bacterial translocation (16S rRNA, LPS binding protein), inflammasome activation (NLRP3, Caspase 1, IL1beta, IL18), Th1 (IL12p35, TNFalpha), Th2 (IL5, IL13, GATA3, CCL11, CCL17), Th17 (IL17A, IL17RC, IL17RC, IL23, IL23R, IL6), Treg (IL10, TGFbeta), myofibroblast activation (alphaSMA, Vimentin) and collagen deposition (type I, III and VI). Bacterial translocation, inflammasome activation, Th2, and Th17 cytokines correlated with myofibroblast activation, collagen deposition, and fibrosis staged by ultrasound. Liver fibrosis in hepatosplenic schistosomiasis is associated not only with Th2 response but also with NLRP3 inflammasome activation and Th17 immune response, probably exacerbated by bacterial translocation. Dual targeting of IL13/IL17 may benefit patients with severe disease.

Palavras-chave

Schistosomiasis mansoni, immune response, bacterial translocation, NLRP3 inflammasome, liver fibrosis

Agradecimentos

CNPq, NIH