Publikationsdatenbank

Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells (2023)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Le‐Trilling, Vu Thuy Khanh

Ebel, Jana‐Fabienne

Baier, Franziska

Wohlgemuth, Kerstin

Pfeifer, Kai Robin

Mookhoek, Aart

Krebs, Philippe

Determann, Madita

Katschinski, Benjamin

Adamczyk, Alexandra

Lange, Erik

Klopfleisch, R (WE 12)

Lange, Christian M.

Sokolova, Viktoriya

Trilling, Mirko

Westendorf, Astrid M.

Quelle

European journal of immunology : basic, clinical, translational

Bandzählung: 53

Heftzählung: 2

Seiten: Artikel 2249940

ISSN: 1521-4141

Sprache

Englisch

Verweise

URL (Volltext): https://onlinelibrary.wiley.com/doi/10.1002/eji.202249940

DOI: 10.1002/eji.202249940

Pubmed: 36250419

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis.