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Commensal Escherichia coli Strains Can Promote Intestinal Inflammation via Differential Interleukin-6 Production
Ist Teil von
Frontiers in immunology, 2018-10, Vol.9, p.2318-2318
Ort / Verlag
Switzerland: Frontiers Research Foundation
Erscheinungsjahr
2018
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
is a facultative anaerobic symbiont found widely among mammalian gastrointestinal tracts. Several human studies have reported increased commensal
abundance in the intestine during inflammation; however, host immunological responses toward commensal
during inflammation are not well-defined. Here, we show that colonization of gnotobiotic mice with different genotypes of commensal
isolated from healthy conventional microbiota mice and representing distinct populations of
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
strains of Sequence Type 129 (ST129) and ST375 following DSS administration. In contrast, colonization with
strains ST150 and ST468 caused mild intestinal inflammation and triggered only low levels of pro-inflammatory cytokines, a response indistinguishable from that of
-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
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.