Clostridium perfringens Source:: Wikimedia commons, CDC

Another example of commensal microbes that affect host immunity may hold implications for the treatment of autoimmune diseases and other ailments

[Published 23rd December 2010 07:00 PM GMT]


The-Scientist.com, December 23, 2010, by Jeff Akst  —  An abundant type of bacteria that resides in the intestines is critical for keeping the immune system of the colon in check, according to a study published online today (December 23) in ScienceExpress. The results add to the growing body of literature that commensal microbes in the gut are key regulators of host immunity, and may provide potential therapeutic avenues for inflammatory bowel disease (IBD), allergies, and autoimmune diseases.

“This is a big step forward in understanding how the commensal microbiota shapes the host immune system,” immunologist Paul Forsythe of McMaster University in Ontario, who was not involved in the study, told The Scientist in an email. “These results suggest that not only are there specific immune responses to distinct bacterial species, but that these responses are region-specific within the intestine.”

The new study provides “tantalizing data that fits with the story,” he said. “That some bugs are important for one type of immunity and other bugs are important for another type of immunity, and it’s really the balance of these bugs that gives the perfect immune system.”

Over the past several years, evidence has been accumulating that the gut microbiome affects the balanced host immune system. Segmented filamentous bacteria (SFB), for example, appear to induce the production of intestinal Th17 cells, helper T cells that are critical to fighting pathogens.

Too many Th17 cells, however, can promote autoimmunity without the proper balance of regulatory T cells (Tregs) to suppress the immune response against one’s own cells. To see whether certain commensal bacterial species might regulate the production of Tregs in the intestines, immunologist Kenya Honda of the University of Tokyo and his colleagues compared normal mice to germ-free mice that harbored no bacteria. They found no major differences in the the small intestine, but significantly fewer Tregs in the colon, suggesting that the missing bacteria may be inducing Treg production.

Antibiotic and chloroform-based tests revealed that the responsible microbes were likely spore-forming, Gram-positive bacteria. As Clostridia are one of the most abundant gut bacteria that fit this description, Honda and his colleagues colonized germ-free mice with a cocktail of 46 different strains of Clostridia. The results confirmed their suspicion — the bacterial treatment resulted in the accumulation of Tregs in the colon. Treg levels in the small intestine did not change, however, suggesting that Clostridia only affect the production of Tregs in the lower part of the digestive tract.

“This is one of the first studies that identifies a specific example of a commensal microbe affecting regulatory T cells,” said coauthor Ivaylo Ivanov, an immunologist at the Columbia University Medical Center in New York. There was a study published earlier this year, he noted, that suggested another bacteria, Bacteroides fragilis, could also induce Treg production in the gut, but those researchers “saw a very marginal induction of regulatory T cells,” said Ivanov, who collaborated on the research while at New York University School of Medicine. “This study identifies Clostridia as a really strong inducer.”

To read more, please click on this hot link…….. New gut bacteria regulate immunity – The Scientist – Magazine of the Life Sciences

http://www.the-scientist.com/news/display/57901/#ixzz18y6S9tYD

K. Atarashi, et al., “Induction of colonic regulatory T cells by indigenous Clostridium species,” ScienceExpress, 10.1126/science. 1198469, 2010.

Published Online 23 December 2010
< Science Express Index
Science DOI: 10.1126/science.1198469

  • Report

Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species

1. Koji Atarashi1,*,

2. Takeshi Tanoue1,*,

3. Tatsuichiro Shima2,

4. Akemi Imaoka2,

5. Tomomi Kuwahara3,

6. Yoshika Momose4,

7. Genhong Cheng6,

8. Sho Yamasaki7,

9. Takashi Saito7,

10. Yusuke Ohba9,

11. Tadatsugu Taniguchi1,

12. Kiyoshi Takeda5,

13. Shohei Hori8,

14. Ivaylo I. Ivanov10,

15. Yoshinori Umesaki2,

16. Kikuji Itoh4 and

17. Kenya Honda1,11,

+ Author Affiliations

1.       1Department of Immunology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
2.       2Yakult Central Institute for Microbiological Research, Tokyo 186-8650, Japan.
3.       3Department of Molecular Bacteriology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
4.       4Department of Veterinary Public Health, The University of Tokyo, Tokyo 113-8657, Japan.
5.       5Laboratory of Immune Regulation, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
6.       6Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095–1781, USA.
7.       7Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
8.       8Research Unit for Immune Homeostasis, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan.
9.       9Laboratory of Pathophysiology and Signal Transduction, Graduate School of Medicine, Hokkaido University, Sapporo 060-0815, Japan.
10.   10Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
11.   11Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama 332-0012, Japan.

1.          To whom correspondence should be addressed. E-mail: kenya@m.u-tokyo.ac.jp

1.          * These authors contributed equally to this work.

Abstract

CD4+ T regulatory cells (Tregs), expressing the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, Tregs were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota—particularly clusters IV and XIVa of the genus Clostridium—promoted Treg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor–β (TGF-β) and affected Foxp3+ Treg number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic IgE responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.

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