Hepatic macrophages play critical roles in the establishment and growth of hydatid cysts in the liver during Echinococcus granulosus sensu stricto infection

Abstract

Cystic echinococcosis (CE) is a worldwide neglected zoonotic disease caused by infection with the larval stage of the tapeworm Echinococcus granulosus sensu lato (E. granulosus s.l.), which predominantly resides in the liver accompanied by mild inflammation. Macrophages constitute the main cellular component of the liver and play a central role in controlling the progression of inflammation and liver fibrosis. However, the role of hepatic macrophages in the establishment and growth of hydatid cysts in the liver during E. granulosus sensu stricto (E. granulosus s.s.) infection has not been fully elucidated. Here, we showed that CD68+ macrophages accumulated in pericystic areas of the liver and that the expression of CD163, a marker of anti-inflammatory macrophages, was more evident in active CE patients than in inactive CE patients. Moreover, in a mouse model of E. granulosus s.s. infection, the pool of hepatic macrophages expanded dramatically through the attraction of massive amounts of monocyte-derived macrophages (MoMFs) to the infection site. These infiltrating macrophages preferentially polarized toward an iNOS+ proinflammatory phenotype at the early stage and then toward a CD206+ anti-inflammatory phenotype at the late stage. Notably, the resident Kupffer cells (KCs) predominantly maintained an anti-inflammatory phenotype to favor persistent E. granulosus s.s. infection. In addition, depletion of hepatic macrophages promoted E. granulosus s.s. larval establishment and growth partially by inhibiting CD4+ T-cell recruitment and liver fibrosis. The above findings demonstrated that hepatic macrophages play a vital role in the progression of CE, contributing to a better understanding of the local inflammatory responses surrounding hydatid cysts and possibly facilitating the design of novel therapeutic approaches for CE.

Liver Histopathological and Immunohistochemical Evaluation from Fasciola hepatica Experimentally Infected and Reinfected Sheep

“…M2 macrophages may play a role in the proliferation of fibrous connective tissue surrounding granulomas in F. hepatica infections in sheep [ 19 ] and biliary fibrosis in cattle [ 48 ]. F. gigantica has also been shown to induce M2 macrophage activation in mice, which has been related to hepatic fibrosis [ 49 ]. In other helminth infections such as Echinococcus granulosus and E. multilocularis , an M2 macrophage activation has also been reported, which has been related to parasite establishment [ 50 , 51 ].…”