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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-? 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.

SUBMITTER: Kittana H 

PROVIDER: S-EPMC6189283 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Commensal <i>Escherichia coli</i> Strains Can Promote Intestinal Inflammation via Differential Interleukin-6 Production.

Kittana Hatem H   Gomes-Neto João Carlos JC   Heck Kari K   Geis Abby L AL   Segura Muñoz Rafael R RR   Cody Liz A LA   Schmaltz Robert J RJ   Bindels Laure B LB   Sinha Rohita R   Hostetter Jesse M JM   Benson Andrew K AK   Ramer-Tait Amanda E AE  

Frontiers in immunology 20181009


<i>Escherichia coli</i> is a facultative anaerobic symbiont found widely among mammalian gastrointestinal tracts. Several human studies have reported increased commensal <i>E. coli</i> abundance in the intestine during inflammation; however, host immunological responses toward commensal <i>E. coli</i> during inflammation are not well-defined. Here, we show that colonization of gnotobiotic mice with different genotypes of commensal <i>E. coli</i> isolated from healthy conventional microbiota mice  ...[more]

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