Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota

Authors

Hachung Chung, Brigham and Women’s Hospital
Sünje J. Pamp, Stanford University School of MedicineFollow
Jonathan A. Hill, Harvard Medical School
Neeraj K. Surana, Brigham and Women’s HospitalFollow
Sanna M. Edelman, Brigham and Women’s Hospital
Erin B. Troy, Brigham and Women’s Hospital
Nicola C. Reading, Brigham and Women’s Hospital
Eduardo J. Villablanca, Harvard Medical School
Sen Wang, Harvard Medical School
Jorge R. Mora, Harvard Medical SchoolFollow
Yoshinori Umesaki, Yakult Central Institute for Microbiological Research
Diane Mathis, Harvard Medical SchoolFollow
Christophe Benoist, Harvard Medical SchoolFollow
David A. Relman, Stanford University School of MedicineFollow
Dennis L. Kasper, Brigham and Women’s HospitalFollow

Date of this Version

6-20-2012

Document Type

Article

Citation

Cell 149, 1578–1593, June 22, 2012; DOI 10.1016/j.cell.2012.04.037

Abstract

Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4⁺ and CD8⁺ T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression—all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system.