Autophagy Activated by Peroxiredoxin of Entamoeba histolytica.

Xia Li,Meng Feng,Hang Zhou,Yanqing Zhao,Hiroshi Tachibana,Ke Qiao,Xunjia Cheng,Yuhan Zhang

doi:10.3390/cells9112462

Xia Li, Meng Feng + Show 6 more

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https://doi.org/10.3390/cells9112462

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Abstract

Autophagy, an evolutionarily conserved mechanism to remove redundant or dangerous cellular components, plays an important role in innate immunity and defense against pathogens, which, in turn, can regulate autophagy to establish infection within a host. However, for Entamoeba histolytica, an intestinal protozoan parasite causing human amoebic colitis, the interaction with the host cell autophagy mechanism has not been investigated. In this study, we found that E. histolytica peroxiredoxin (Prx), an antioxidant enzyme critical for parasite survival during the invasion of host tissues, could activate autophagy in macrophages. The formation of autophagosomes in macrophages treated with recombinant Prx of E. histolytica for 24 h was revealed by immunofluorescence and immunoblotting in RAW264.7 cells and in mice. Prx was cytotoxic for RAW264.7 macrophages after 48-h treatment, which was partly attributed to autophagy-dependent cell death. RNA interference experiments revealed that Prx induced autophagy mostly through the toll-like receptor 4 (TLR4)–TIR domain-containing adaptor-inducing interferon (TRIF) pathway. The C-terminal part of Prx comprising 100 amino acids was the key functional domain to activate autophagy. These results indicated that Prx of E. histolytica could induce autophagy and cytotoxic effects in macrophages, revealing a new pathogenic mechanism activated by E. histolytica in host cells.

Highlights

Entamoeba histolytica is a protozoan parasite that causes human amoebic colitis and amoebic liver abscess (ALA); it infects 50 million people annually, causing 40,000–100,000 deaths [1]
The results indicate that the recombinant protein (Eh-rPrx) could induce macrophage autophagy accompanied by autophagy-dependent cell death (ADCD)
This study reveals, for the first time, that E. histolytica Prx (Eh-Prx) is capable of inducing autophagy in immune cells, which is important for further understanding of E. histolytica pathogenesis and the role of autophagy in infection

Summary

Introduction

Entamoeba histolytica is a protozoan parasite that causes human amoebic colitis and amoebic liver abscess (ALA); it infects 50 million people annually, causing 40,000–100,000 deaths [1]. People are infected by ingesting food and water contaminated by amoeba cysts. 90% of infected individuals are asymptomatic but in 10%, amoeba trophozoites, driven by unknown stimuli, can penetrate the mucosal barrier of the colon and invade the intestinal lamina propria, leading to amoebic diarrhea and colitis, or even ALA if trophozoites disseminate through the portal circulation [2]. As a facultative anaerobic organism, E. histolytica requires high amounts of Prx to resist oxidative damage during invasion of host tissues and organs [4,5].

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