P072 TREM-1 stimulation ameliorates colitis in mice
H. W. Ma*1, 2, X. Che1, 2, D. H. Seo1, 2, J. H. Kim1, 2, D. H. Kim1, T. I. Kim1, W. H. Kim1, S. W. Kim1, 2, 3, J. H. Cheon1, 2, 3
1Yonsei University College of Medicine, Department of Internal Medicine and Institute of Gastroenterology, Seoul, South Korea, 2Yonsei University College of Medicine, Brain Korea 21 PLUS Project for Medical Science, Seoul, South Korea, 3Yonsei University College of Medicine, Severance Biomedical Science Institute, Seoul, South Korea
TREM- 1 ligation with an agonist antibody induces cytokine production in monocytes, and promotes antimicrobial functions of neutrophils. Further, TREM-1 ligation strongly enhances inflammatory responses to bacterial compounds, which leads to enhance bacterial clearance and promotes resolution of infection. TREM-1 has been shown to be underexpressed in macrophages in the human intestine, which is constantly exposed to the gut bacteria, thus implying their capacity to control the gut microbiome.
Mouse colitis was induced by the administration of TNBS into the colon or by DSS via oral route. A TREM-1 agonist (Anti-TREM-1 antibody) was injected into the mouse anus and/or i.p., and body weight, colon length, and disease activity index were checked. The histopathology, bacterial load, and mechanisms of the TREM-1 agonist on mouse colitis were examined by using H&E staining, bacterial counting, 16S RNA sequencing, and immunofluorescence.
TREM-1 agonist administration into both the anus and i.p. of mouse ameliorates body weight changes, colon length shortening, and DAI in TNBS-induced mouse colitis. Consistently, TREM-1 agonist i.p. injection prevented DSS-induced colitis. TREM-1 ameliorates histopathology of colon by colitis and suppressed infiltration of macrophage in the colon tissues. TREM-1 agonist-treated colon tissues showed downregulated NF-κB signalling and enhanced bacterial clearance by macrophages, which were mediated through macrophage modulation by the TREM-1 agonist
TREM-1 agonist prevents mouse colitis. Together, these experiments highlight the importance of NF-kB and TREM-1 in the maintenance of intestinal homeostasis through enhanced bacterial clearance.