Fasciola hepatica: MR and Dectin-1 participate in the modulation of peritoneal macrophages during early stage of the infection

GUASCONI, L; SERRADELL, MC; MASIH, DT

Congreso; First French-Argentine Immunology Congress -LVIII Reuni¡§®n Anual de la Sociedad Argentina de Inmunolog¡§ªa, XII Jornada Cient¡§ªfica del Grupo Rioplatense de Citometr¡§ªa de Flujo y 3º Jornadas Argentinas de Inmunodeficiencias Pri; 2010

Fasciolosis is becoming a serious public health problem in humans. Fasciola hepatica releases excretory?secretory products (ESP), and the interaction of these products with peritoneal macrophages (pMФ) is crucial in the early stage of the infection. In previous results we observed that pMФ from naive Balb/c mice stimulated with ESP presented increased arginase activity and Arg I expression, high levels of TGF-β and IL-10 production. A partial reversion in these effects was observed when pMФ were pre-incubated with Mannan (Man), anti-MR, Laminarin (Lam), or anti-Dectin-1, and then stimulated with ESP; as well as in pMФ stimulated with ESP pre-treated with α-Mannosidase. So, we suggested the participation of at least two C-type lectin receptors (CLRs), MR and Dectin-1, in the interaction of ESP with pMФ. In this work we evaluated the behavior of pMФ during the early state of the infection, and we observed that increased arginase activity and Arginase-I expression (p<0.018 and p<0.05 respectively), as well as high levels in the IL-10 and TGF-β production (p<0.020 and p<0.027 respectively) compare with control group were induced on pMФ obtained from mice challenged with F.hepatica metacercariae (48 h after infection). To evaluate if MR and Dectin-1 participate in the phenotypic changes observed in pMФ during early state of the infection, we injected mice ip with Man or Lam before the infection. We could observed a partial reversion in the increased arginase activity (p<0.05 to both, Lam and Man), as well as in the high levels of IL-10 (p<0.05 to both, Lam and Man) and TGF-β (p<0.05 to Lam, p<0.001 to Man) production. Therefore, taking into account in vitro and in vivo results, we can conclude that at least two CLRs, MR and Dectin-1, participate in the interaction of F.hepatica products with pMФ, allowing this parasite to induce immunoregulatory effects on these innate immune cells, which would constitute a crucial event for extend their survival in the host.