Open AccessTLR9 limits enteric antimicrobial responses and promotes microbiota‐based colonisation resistance during Citrobacter rodentium infection
Author(s) -
Yang Hyungjun,
Yu Hong B.,
Bhinder Ganive,
Ryz Natasha R.,
Lee Julia,
Yang Hong,
Fotovati Abbas,
Gibson Deanna L.,
Turvey Stuart E.,
Reid Gregor S.,
Vallance Bruce A.
Publication year - 2019
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.13026
Subject(s) - citrobacter rodentium , biology , microbiology and biotechnology , colonisation resistance , tlr9 , citrobacter , pathogen , antimicrobial , enteropathogenic escherichia coli , gut flora , immune system , immunology , antibiotics , enterobacteriaceae , escherichia coli , biochemistry , gene expression , gene , dna methylation
Mammalian cells express an array of toll‐like receptors to detect and respond to microbial pathogens, including enteropathogenic and enterohemorrhagic E scherichia coli (EPEC and EHEC). These clinically important attaching and effacing (A/E) pathogens infect the apical surface of intestinal epithelial cells, causing inflammation as well as severe diarrheal disease. Because EPEC and EHEC are human‐specific, the related murine pathogen Citrobacter rodentium has been widely used to define how hosts defend against A/E pathogens. This study explored the role of TLR9, a receptor that recognises unmethylated CpG dinucleotides present in bacterial DNA, in promoting host defence against C. rodentium . Infected Tlr9 −/− mice suffered exaggerated intestinal damage and carried significantly higher (10–100 fold) pathogen burdens in their intestinal tissues as compared with wild type (WT) mice. C. rodentium infection also induced increased antimicrobial responses, as well as hyperactivation of NF‐κB signalling in the intestines of Tlr9 −/− mice. These changes were associated with accelerated depletion of the intestinal microbiota in Tlr9 −/− mice as compared with WT mice. Notably, antibiotic‐based depletion of the gut microbiota in WT mice prior to infection increased their susceptibility to the levels seen in Tlr9 −/− mice. Our results therefore indicate that TLR9 signalling suppresses intestinal antimicrobial responses, thereby promoting microbiota‐mediated colonisation resistance against C. rodentium infection.