Publikationsdatenbank

Endotoxicity of lipopolysaccharide as a determinant of T-cell-mediated colitis induction in mice (2014)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Gronbach, Kerstin

Flade, Isabell

Holst, Otto

Lindner, Buko

Ruscheweyh, Hans Joachim

Wittmann, Alexandra

Menz, Sarah

Schwiertz, Andreas

Adam, Patrick

Stecher, Bärbel

Josenhans, Christine

Suerbaum, Sebastian

Gruber, Achim D (WE 12)

Kulik, Andreas

Huson, Daniel

Autenrieth, Ingo B

Frick, Julia-Stefanie

Quelle

Gastroenterology

Bandzählung: 146

Heftzählung: 3

Seiten: 765 – 775

ISSN: 0016-5085

Sprache

Englisch

Verweise

DOI: 10.1053/j.gastro.2013.11.033

Pubmed: 24269927

Kontakt

Institut für Tierpathologie

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

Abstract / Zusammenfassung

The intestinal microbiota is an important determinant of the mucosal response. In patients with inflammatory bowel diseases, the mucosal immune system has inappropriate interactions with the intestinal microbiota. We investigated how the composition of the intestinal microbiota affects its endotoxicity and development of colitis in mice.

Germ-free C57BL/6J-Rag(1tm1Mom) (Rag1(-/-)) mice were colonized with 2 different types of complex intestinal microbiota. Colitis was induced in Rag1(-/-) mice by transfer of CD4(+)CD62L(+) T cells from C57BL/6J mice. Colonic tissues were collected and used for histologic analysis and cell isolation. Activation of lamina propria dendritic cells and T cells was analyzed by flow cytometry.

After transfer of CD4(+)CD62L(+) T cells, mice with intestinal Endo(lo) microbiota (a low proportion of Enterobacteriaceae, high proportion of Bacteroidetes, and low endotoxicity) maintained mucosal immune homeostasis, and mice with highly endotoxic Endo(hi) microbiota (a high proportion of Enterobacteriaceae and low proportion of Bacteroidetes) developed colitis. To determine whether the effects of Endo(hi) microbiota were related to the higher endotoxic activity of lipopolysaccharide (LPS), we compared LPS from Enterobacteriaceae with that of Bacteroidetes. Administration of Escherichia coli JM83 (wild-type LPS) to the mice exacerbated colitis, and Escherichia coli JM83 + htrBPG (mutated LPS, with lower endotoxicity, similar to that of Bacteroidetes) prevented development of colitis after transfer of the T cells to mice.

The endotoxicity of LPS produced by the intestinal microbiota is a determinant of whether mice develop colitis after transfer of CD4(+)CD62L(+) T cells. This finding might aid the design of novel biologics or probiotics to treat inflammatory bowel disease.