KLF4 upregulation is involved in alternative macrophage activation during secondary <i>Echinococcus granulosus</i> infection

Dong, Di; Chen, Congzhe; Hou, Jun; Yang, Kun; Hairui, Fang; Hongqun, Jiang; Guo, Feng; Wu, Xiangwei; Chen, Xueling

doi:10.1111/pim.12666

Cited by 7 publications

(1 citation statement)

References 40 publications

(72 reference statements)

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“…Furthermore, macrophages can polarize toward various phenotypes when stimulated by the surrounding microenvironment and parasitic infections [15,27,32,33]. Some studies have reported that polarization of peritoneal macrophages toward an antiinflammatory phenotype, thus enabling parasite survival, is also induced in the intraperitoneal infection model of E. granulosus s.s. infection [17,34]. Our findings showed that infiltrated proinflammatory iNOS + MoMFs (M1) accounted for the majority of the massive number of recruited macrophages in the lesion environment during the early stage of cyst establishment in the MD and HD groups; these cells may play an important role in aiding the clearance or killing of PSCs by releasing proinflammatory cytokines or nitric oxide (NO) via NOS-2/iNOS [35], the marker for M1 macrophages [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

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

Wang,

Yu,

Wang

et al. 2023

PLoS Negl Trop Dis

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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.

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