Olfactomedin-4+ neutrophils exacerbate intestinal epithelial damage in Clostridioides difficile infection 2026 Jose et al

[Andy]

ABSTRACT​

Neutrophils are dominant cells during acute immune response to Clostridioides difficile infection (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 (OLFM4+ neutrophils) during CDI. Single-cell transcriptomics reveal that Olfm4 is increased in blood neutrophils of infected mice, and these cells exhibit gene signatures characterized by high expression of degranulation genes. In C. difficile-infected mice, OLFM4+ neutrophils aggregate to areas of severe intestinal epithelial cell (IEC) damage, and plasma OLFM4 was significantly increased in both C. difficile-infected mice and patients. In vitro, OLFM4+ neutrophils and recombinant OLFM4 protein exacerbated C. difficile toxin-induced IEC damage. In sum, our studies provide novel insights into neutrophil-mediated pathology and highlight the role of OLFM4+ neutrophils in worsening CDI-induced IEC damage.

Open access

 

[V.R.T.]

Could this explain the gut issues in MECFS if the OLFM4 link proves genuine?

 

[Jonathan Edwards]

Could this explain the gut issues in MECFS if the OLFM4 link proves genuine?

It might explain why people with an OLFM4 variant had more gut symptoms than others with ME/CFS if they did (I have no idea if the data exist). I am not sure it tells us anything else relevant. We know that OLFM4 is present on some neutrophils and the link to ME/CFS might be because neutrophils are involved but we have little or no evidence for that. Otherwise this is a specific gut infection study that just seems to show OLFM4 neutrophils are involved in the response.

I can't make a lot of it.