학술논문

Bacterial flagellin is a dominant, stable innate immune activator in the gastrointestinal contents of mice and rats
Document Type
article
Source
Gut Microbes, Vol 15, Iss 1 (2023)
Subject
Gut microbiota
LPS
MyD88
toll-like Receptor-5
toll-like Receptor-4
cytokines
Diseases of the digestive system. Gastroenterology
RC799-869
Language
English
ISSN
19490976
1949-0984
1949-0976
Abstract
ABSTRACTIntestinal contents comprise the largest repository of immunogenic ligands of microbial origin. We undertook this study to assess the predominant microbe-associated molecular patterns (MAMPs) present therein and the receptors) that mediate the innate immune responses to them. Here, we demonstrated that intestinal contents from conventional, but not germ-free, mice and rats triggered robust innate immune responses in vitro and in vivo. Such immune responses were abrogated in the absence of either myeloid differentiation factor 88 (MyD88) or Toll-like receptor (TLR) 5, but not TLR4, suggesting that the stimuli was flagellin (i.e., protein subunit of flagella that drives bacterial motility). Accordingly, pre-treating intestinal extracts with proteinase, thereby degrading flagellin, was sufficient to block their ability to activate innate immune responses. Taken together, this work serves to underscore flagellin as a major, heat-stable and bioactive MAMP in the intestinal content that confers this milieu strong potential to trigger innate immune responses.