Commensal Escherichia coli Strains Can Promote Intestinal Inflammation via Differential Interleukin-6 Production.

Abstract

Escherichia coli is a facultative anaerobic symbiont found widely among mammalian gastrointestinal tracts. Several human studies have reported increased commensal E. coli abundance in the intestine during inflammation; however, host immunological responses toward commensal E. coli during inflammation are not well-defined. Here, we show that colonization of gnotobiotic mice with different genotypes of commensal E. coli isolated from healthy conventional microbiota mice and representing distinct populations of E. coli elicited strain-specific disease phenotypes and immunopathological changes following treatment with the inflammatory stimulus, dextran sulfate sodium (DSS). Production of the inflammatory cytokines GM-CSF, IL-6, and IFN-γ was a hallmark of the severe inflammation induced by E. coli strains of Sequence Type 129 (ST129) and ST375 following DSS administration. In contrast, colonization with E. coli strains ST150 and ST468 caused mild intestinal inflammation and triggered only low levels of pro-inflammatory cytokines, a response indistinguishable from that of E. coli-free control mice treated with DSS. The disease development observed with ST129 and ST375 colonization was not directly associated with their abundance in the GI tract as their levels did not change throughout DSS treatment, and no major differences in bacterial burden in the gut were observed among the strains tested. Data mining and in vivo neutralization identified IL-6 as a key cytokine responsible for the observed differential disease severity. Collectively, our results show that the capacity to exacerbate acute intestinal inflammation is a strain-specific trait that can potentially be overcome by blocking the pro-inflammatory immune responses that mediate intestinal tissue damage.

• Authors: Hatem Kittana, João Carlos Gomes-Neto, Kari Heck, Abby L Geis, Rafael R Segura Muñoz, Liz A Cody, Robert J Schmaltz, Laure B Bindels, Rohita Sinha, Jesse M Hostetter, Andrew K Benson, Amanda E Ramer-Tait
• Journal: Frontiers in immunology (Front Immunol) Vol. 9 Pg. 2318 ( 2018) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 30356663 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-6

Topics

• Animals
• Biopsy
• Cytokines (biosynthesis)
• Disease Models, Animal
• Disease Progression
• Disease Susceptibility
• Enterocolitis (etiology, metabolism, pathology)
• Escherichia coli (classification, genetics)
• Female
• Gastrointestinal Microbiome (immunology)
• Immunomodulation
• Interleukin-6 (biosynthesis, metabolism)
• Intestinal Mucosa (immunology, metabolism, microbiology, pathology)
• Male
• Mice
• Multilocus Sequence Typing
• Phylogeny