Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published April 22, 2010 | Accepted Version + Supplemental Material
Journal Article Open

A Pathobiont of the Microbiota Balances Host Colonization and Intestinal Inflammation

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

Files

mmc1.pdf
Files (27.1 MB)
Name Size Download all
md5:7d8b31af82f1bf777de6c6d9cbc9fdd5
645.8 kB Preview Download
md5:07a2e716ff744f062165591fb1ecdd13
4.5 MB Preview Download
md5:d3f788c7053fdb45b45a5b50534a19af
7.1 MB Download
md5:d3b0ebf2430a835b9062436fa85861eb
7.1 MB Download
md5:432b1cf71cd019f887fd01e9ea500813
759.8 kB Download
md5:df9a94dad0c67dc5bd3b59400040f1d2
7.1 MB Download

Additional details

Created:
August 21, 2023
Modified:
October 20, 2023