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.