Olfactomedin-4neutrophils exacerbate intestinal epithelial damage ininfection.

Abstract

Neutrophils are dominant cells during acute immune response toinfection (CDI). A higher number of infiltrating colonic neutrophils is clearly linked to greater tissue damage and severe CDI (3, 4). However, the mechanism(s) by which neutrophils exacerbate tissue damage in CDI remain unknown. We investigated the role of a neutrophil subset marked by Olfactomedin-4 expression (OLFM4neutrophils) during CDI. Single-cell transcriptomics reveal thatis increased in blood neutrophils of infected mice, and these cells exhibit gene signatures characterized by high expression of degranulation genes. In-infected mice, OLFM4neutrophils aggregate to areas of severe intestinal epithelial cell (IEC) damage, and plasma OLFM4 was significantly increased in both-infected mice and patients., OLFM4neutrophils and recombinant OLFM4 protein exacerbatedtoxin-induced IEC damage. In sum, our studies provide novel insights into neutrophil-mediated pathology and highlight the role of OLFM4neutrophils in worsening CDI-induced IEC damage.