BACKGROUND: Serologic expression cloning has identified flagellins of the intestinal microbiota as immunodominant antigens in experimental colitis in mice and in individuals with Crohn's disease (CD). The present study was done to identify the microbial source of such flagellins. METHODS: Using a variety of isolation and culture approaches, a number of previously unknown flagellated bacteria were isolated. Based on 16S ribosomal DNA sequences, these bacteria fall into the family Lachnospiraceae of the phylum Firmicutes. RESULTS: Serum IgG from patients with CD and from mice with colitis reacted to the flagellins of these bacteria, and only their flagellins, whereas serum IgG from controls did not. The sequence of these flagellins demonstrate conserved amino- and carboxy-terminal domains that cluster phylogenetically and have a predicted 3D structure similar to Salmonella fliC, including an intact TLR5 binding site. The flagellin of 1 of these bacteria was likely O-glycosylated. CONCLUSIONS: The conserved immune response in both mouse and human to these previously unknown flagellins of the microbiota indicate that they play an important role in host-microbe interactions in the intestine.
BACKGROUND: Serologic expression cloning has identified flagellins of the intestinal microbiota as immunodominant antigens in experimental colitis in mice and in individuals with Crohn's disease (CD). The present study was done to identify the microbial source of such flagellins. METHODS: Using a variety of isolation and culture approaches, a number of previously unknown flagellated bacteria were isolated. Based on 16S ribosomal DNA sequences, these bacteria fall into the family Lachnospiraceae of the phylum Firmicutes. RESULTS: Serum IgG from patients with CD and from mice with colitis reacted to the flagellins of these bacteria, and only their flagellins, whereas serum IgG from controls did not. The sequence of these flagellins demonstrate conserved amino- and carboxy-terminal domains that cluster phylogenetically and have a predicted 3D structure similar to Salmonella fliC, including an intact TLR5 binding site. The flagellin of 1 of these bacteria was likely O-glycosylated. CONCLUSIONS: The conserved immune response in both mouse and human to these previously unknown flagellins of the microbiota indicate that they play an important role in host-microbe interactions in the intestine.
Authors: Philipp Rausch; Ateequr Rehman; Sven Künzel; Robert Häsler; Stephan J Ott; Stefan Schreiber; Philip Rosenstiel; Andre Franke; John F Baines Journal: Proc Natl Acad Sci U S A Date: 2011-11-08 Impact factor: 11.205
Authors: Jingxiao Ye; Jimmy W Lee; Laura L Presley; Elizabeth Bent; Bo Wei; Jonathan Braun; Neal L Schiller; Daniel S Straus; James Borneman Journal: Inflamm Bowel Dis Date: 2008-08 Impact factor: 5.325
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Authors: Xiaochang Xue; Anthony T Cao; Xiaocang Cao; Suxia Yao; Eric D Carlsen; Lynn Soong; Chang-Gong Liu; Xiuping Liu; Zhanju Liu; L Wayne Duck; Charles O Elson; Yingzi Cong Journal: Eur J Immunol Date: 2014-01-13 Impact factor: 5.532