Enterogenous Bacterial Glycolipids Are Required for the Generation of Natural Killer T Cells Mediated Liver Injury

Overview

Journal Sci Rep

Specialty Science

Date 2016 Nov 9

PMID 27821872

Citations 26

Authors

YingFeng Wei

Benhua Zeng

Jianing Chen

Guangying Cui

Chong Lu

Wei Wu

Jiezuan Yang

Hong Wei

Rufeng Xue

Li Bai

Zhi Chen

Lanjuan Li

Kazuya Iwabuchi

Toshimitsu Uede

Luc Van Kaer

Hongyan Diao

Affiliations

Soon will be listed here.

Abstract

Glycolipids are potent activator of natural killer T (NKT) cells. The relationship between NKT cells and intestinal bacterial glycolipids in liver disorders remained unclear. We found that, in sharp contrast to specific pathogen-free (SPF) mice, germ-free (GF) mice are resistant to Concanavalin A (ConA)-induced liver injury. ConA treatment failed to trigger the activation of hepatic NKT cells in GF mice. These defects correlated with the sharply reduced levels of CD1d-presented glycolipid antigens in ConA-treated GF mice compared with SPF counterparts. Nevertheless, CD1d expression was similar between these two kinds of mice. The absence of intestinal bacteria did not affect the incidence of αGalCer-induced liver injury in GF mice. Importantly, we found the intestinal bacteria contain glycolipids which can be presented by CD1d and recognized by NKT cells. Furthermore, supplement of killed intestinal bacteria was able to restore ConA-mediated NKT cell activation and liver injury in GF mice. Our results suggest that glycolipid antigens derived from intestinal commensal bacteria are important hepatic NKT cell agonist and these antigens are required for the activation of NKT cells during ConA-induced liver injury. These finding provide a mechanistic explanation for the capacity of intestinal microflora to control liver inflammation.

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