A Pathobiont of the Microbiota Balances Host Colonization and Intestinal Inflammation
- Creators
- Chow, Janet
-
Mazmanian, Sarkis K.
Abstract
The gastrointestinal tract harbors a diverse microbiota that has coevolved with mammalian hosts. Though most associations are symbiotic or commensal, some resident bacteria (termed pathobionts) have the potential to cause disease. Bacterial type VI secretion systems (T6SSs) are one mechanism for forging host-microbial interactions. Here we reveal a protective role for the T6SS of Helicobacter hepaticus, a Gram-negative bacterium of the intestinal microbiota. H. hepaticus mutants with a defective T6SS display increased numbers within intestinal epithelial cells (IECs) and during intestinal colonization. Remarkably, the T6SS directs an anti-inflammatory gene expression profile in IECs, and CD4+ T cells from mice colonized with T6SS mutants produce increased interleukin-17 in response to IECs presenting H. hepaticus antigens. Thus, the H. hepaticus T6SS limits colonization and intestinal inflammation, promoting a balanced relationship with the host. We propose that disruption of such balances contributes to human disorders such as inflammatory bowel disease and colon cancer.
Additional Information
© 2010 Elsevier. Received 18 October 2009; revised 2 February 2010; accepted 1 March 2010. Published: April 21, 2010. Available online 21 April 2010. We thank Diana Perez and Rochelle Diamond for help with cell sorting, Vijaya Rao and Igor Antoshechkin of the Millard and Muriel Jacobs Genetics and Genomics Laboratory for the microarray studies, and the Beckman Imaging Center at Caltech for use of microscopes. We are grateful to Dr. Rob Maier (University of Georgia) and Stephane Benoit (University of Georgia) for the kind gift of the pSLB167 plasmid, Dr. Dominique Kaiserlian (INSEM, France) for the generous gift of MODE-K cells, and Dr. Vincent T. Young (University of Michigan) for advice on generating mutants. Histopathology analysis was performed by Dr. Roderick T. Bronson (Harvard Medical School). We are grateful to members of the Mazmanian laboratory for their critical review of the manuscript. J.C. is supported by a predoctoral training grant (National Institutes of Health [NIH] GM007616). S.K.M. is a Searle Scholar. This work is supported by funding from the NIH/NIDDK (DK078938), Emerald Foundation, Damon Runyon Cancer Research Foundation, and the Crohn's and Colitis Foundation of America to S.K.M.Attached Files
Accepted Version - nihms187634.pdf
Supplemental Material - mmc1.pdf
Supplemental Material - mmc2.avi
Supplemental Material - mmc3.avi
Supplemental Material - mmc4.avi
Supplemental Material - mmc5.avi
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Additional details
- PMCID
- PMC2859213
- Eprint ID
- 18416
- DOI
- 10.1016/j.chom.2010.03.004
- Resolver ID
- CaltechAUTHORS:20100525-082828564
- NIH Predoctoral Fellowship
- GM007616
- NIH
- DK078938
- Emerald Foundation
- Damon Runyon Cancer Research Foundation
- Crohn's and Colitis Foundation of America
- Searle Scholars Program
- National Institute of Diabetes and Digestive and Kidney Diseases
- Created
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2010-05-25Created from EPrint's datestamp field
- Updated
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2021-11-08Created from EPrint's last_modified field