TY - JOUR
T1 - A single strain of Clostridium butyricum induces intestinal IL-10-producing macrophages to suppress acute experimental colitis in mice
AU - Hayashi, Atsushi
AU - Sato, Toshiro
AU - Kamada, Nobuhiko
AU - Mikami, Yohei
AU - Matsuoka, Katsuyoshi
AU - Hisamatsu, Tadakazu
AU - Hibi, Toshifumi
AU - Roers, Axel
AU - Yagita, Hideo
AU - Ohteki, Toshiaki
AU - Yoshimura, Akihiko
AU - Kanai, Takanori
N1 - Funding Information:
We thank Dr. Kenya Honda (University of Tokyo) for kindly providing Il10 Venus mice. We thank Drs. Tango Handa, Shinta Mizuno, Kayoko Kimura, Atsuhiro Matsumoto, Keiichiro Saigusa, Yuuichi Ono, Hitoshi Kotani, Shoichi Date, Mina Kitazume, and Miho Takabe (Keio University) and Nobuyuki Onai (Tokyo Medical and Dental University) for technical assistance and Drs. Tomohisa Sujino, Makoto Naganuma, and Tomoharu Yajima for valuable discussion. This study was supported in part by grants-in-aid for Scientific Research, Scientific Research on Priority Areas, Exploratory Research, and Creative Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology; the Japanese Ministry of Health, Labour and Welfare; and the Keio University Medical Fund. A.H. was supported by Miyarisan Pharmaceutical. Y.M. was supported by Research Fellowships of Japan Society for the Promotion of Science for Young Scientist. A.H., Y.M., K.M., and T. Hisamatsu performed the experiments. A.R., H.Y., and T.O. contributed reagents and analysis tools. T.S., N.K., T. Hibi, A.Y., and T.K. conceived and designed the experiments and wrote the paper. A.H. is an employee of Miyarisan Pharmaceutical.
PY - 2013/6/12
Y1 - 2013/6/12
N2 - Imbalance in gut bacterial composition provokes host proinflammatory responses causing diseases such as colitis. Colonization with a mixture of Clostridium species from clusters IV and XIVa was shown to suppress colitis through the induction of IL-10-producing regulatory T (Treg) cells. We demonstrate that a distinct Clostridium strain from cluster I, Clostridium butyricum (CB), prevents acute experimental colitis in mice through induction of IL-10, an anti-inflammatory cytokine. However, while CB treatment had no effect on IL-10 production by T cells, IL-10-producing F4/80+CD11b +CD11cint macrophages accumulated in the inflamed mucosa after CB treatment. CB directly triggered IL-10 production by intestinal macrophages in inflamed mucosa via the TLR2/MyD88 pathway. The colitis-preventing effect of CB was negated in macrophage-specific IL-10-deficient mice, suggesting that induction of IL-10 by intestinal macrophages is crucial for the probiotic action of CB. Collectively, CB promotes IL-10 production by intestinal macrophages in inflamed mucosa, thereby preventing experimental colitis in mice.
AB - Imbalance in gut bacterial composition provokes host proinflammatory responses causing diseases such as colitis. Colonization with a mixture of Clostridium species from clusters IV and XIVa was shown to suppress colitis through the induction of IL-10-producing regulatory T (Treg) cells. We demonstrate that a distinct Clostridium strain from cluster I, Clostridium butyricum (CB), prevents acute experimental colitis in mice through induction of IL-10, an anti-inflammatory cytokine. However, while CB treatment had no effect on IL-10 production by T cells, IL-10-producing F4/80+CD11b +CD11cint macrophages accumulated in the inflamed mucosa after CB treatment. CB directly triggered IL-10 production by intestinal macrophages in inflamed mucosa via the TLR2/MyD88 pathway. The colitis-preventing effect of CB was negated in macrophage-specific IL-10-deficient mice, suggesting that induction of IL-10 by intestinal macrophages is crucial for the probiotic action of CB. Collectively, CB promotes IL-10 production by intestinal macrophages in inflamed mucosa, thereby preventing experimental colitis in mice.
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U2 - 10.1016/j.chom.2013.05.013
DO - 10.1016/j.chom.2013.05.013
M3 - Article
C2 - 23768495
AN - SCOPUS:84879109909
SN - 1931-3128
VL - 13
SP - 711
EP - 722
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 6
ER -