Absence of toll-like receptor 7 ameliorates survival and reduces intestinal injury in mice after Clostridium difficile infection

Clostridioides difficile (CD) is a major cause of antibiotic-associated diarrhea and pseudomembranous enteritis. C. difficile infection (CDI) is increasingly present in the community and represents a significant burden on the healthcare system. Identification of novel immune-based therapeutic target...

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Veröffentlicht in:Microbes and infection 2023-11, Vol.25 (8), p.105210, Article 105210
Hauptverfasser: Yu, Renlin, Yang, Zhubin, Liu, Jiayu, Bai, Haobo, Ding, Hao, Xu, Haofeng, Yu, Hanbin, Cao, Ju, Lai, Xiaofei
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container_end_page
container_issue 8
container_start_page 105210
container_title Microbes and infection
container_volume 25
creator Yu, Renlin
Yang, Zhubin
Liu, Jiayu
Bai, Haobo
Ding, Hao
Xu, Haofeng
Yu, Hanbin
Cao, Ju
Lai, Xiaofei
description Clostridioides difficile (CD) is a major cause of antibiotic-associated diarrhea and pseudomembranous enteritis. C. difficile infection (CDI) is increasingly present in the community and represents a significant burden on the healthcare system. Identification of novel immune-based therapeutic targets from a better understanding of their molecular pathogenesis is urgently required. Toll-like receptor 7 (TLR7) is an important pattern recognition receptor and function as an immune sensor that can trigger host defenses against pathogens, but the relationship between TLR7 and CDI remains unknown. Here, we reported that the expression levels of TLR7 increased significantly in patients and mice with CDI. Absence of TLR7 in mice with CDI demonstrated enhanced bacterial clearance of intestinal contents and reduced intestinal inflammation, edema, injury and prolonged the survival. TLR7 loss decreased the concentrations of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IFN-α1 in the intestine and improved tissue damage and inflammation. Flow cytometry and immunofluorescence results indicated that TLR7 enhanced leukocyte recruitment in the infected intestine. In-vitro results have shown that TLR7 impairs the phagocytosis and killing ability of macrophages to CD, prompts reactive oxygen species (ROS) production and accelerates apoptosis. To our knowledge, our study first identified TLR7 as a critical factor that contributes to the immunopathology of CDI, suggesting that targeting TLR7 might serve as a potential treatment for CDI.
doi_str_mv 10.1016/j.micinf.2023.105210
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C. difficile infection (CDI) is increasingly present in the community and represents a significant burden on the healthcare system. Identification of novel immune-based therapeutic targets from a better understanding of their molecular pathogenesis is urgently required. Toll-like receptor 7 (TLR7) is an important pattern recognition receptor and function as an immune sensor that can trigger host defenses against pathogens, but the relationship between TLR7 and CDI remains unknown. Here, we reported that the expression levels of TLR7 increased significantly in patients and mice with CDI. Absence of TLR7 in mice with CDI demonstrated enhanced bacterial clearance of intestinal contents and reduced intestinal inflammation, edema, injury and prolonged the survival. TLR7 loss decreased the concentrations of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IFN-α1 in the intestine and improved tissue damage and inflammation. Flow cytometry and immunofluorescence results indicated that TLR7 enhanced leukocyte recruitment in the infected intestine. In-vitro results have shown that TLR7 impairs the phagocytosis and killing ability of macrophages to CD, prompts reactive oxygen species (ROS) production and accelerates apoptosis. 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Flow cytometry and immunofluorescence results indicated that TLR7 enhanced leukocyte recruitment in the infected intestine. In-vitro results have shown that TLR7 impairs the phagocytosis and killing ability of macrophages to CD, prompts reactive oxygen species (ROS) production and accelerates apoptosis. 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subjects Animals
Clostridioides difficile
Clostridium difficile
Clostridium Infections - microbiology
Enterocolitis, Pseudomembranous - pathology
Humans
Inflammation
Intestinal infection
Mice
Microbiology
Toll-Like Receptor 7
title Absence of toll-like receptor 7 ameliorates survival and reduces intestinal injury in mice after Clostridium difficile infection
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