A host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency
Harnessing the microbiome to benefit human health requires an initial step in determining the identity and function of causative microorganisms that affect specific host physiological functions. We show a functional screen of the bacterial microbiota from mice with low intestinal immunoglobulin A (IgA) levels; we identified a Gram-negative bacterium, proposed as <i>Tomasiella immunophila</i>, that induces and degrades IgA in the mouse intestine. Mice harboring <i>T. immunophila</i> are susceptible to infections and show poor mucosal repair. <i>T. immunophila</i> is auxotrophic for the bacterial cell wall amino sugar N-acetylmuramic acid. It delivers immunoglobulin-degrading proteases into outer membrane vesicles that preferentially degrade rodent antibodies with kappa but not lambda light chains. This work indicates a role for symbionts in immunodeficiency, which might be applicable to human disease.
Authors
- Kevin P. Newhall (ORCID: https://orcid.org/0000-0002-4226-718X)
- Julie Y. Zhou (ORCID: https://orcid.org/0000-0002-1533-5183)
- Vanessa Salazar
- Dylan Lawrence (ORCID: https://orcid.org/0000-0001-6919-8308)
- Thaddeus S. Stappenbeck (ORCID: https://orcid.org/0000-0002-6023-3901)
- Qiuhe Lu (ORCID: https://orcid.org/0000-0002-0202-7448)
- Scott T. Espenschied (ORCID: https://orcid.org/0000-0001-8885-7532)
- Lila S. Nolan (ORCID: https://orcid.org/0000-0002-4185-2686)
- Paul Karell (ORCID: https://orcid.org/0000-0002-7606-6693)
- Mohammed Dwidar (ORCID: https://orcid.org/0000-0003-1366-0393)
- Thomas Clavel (ORCID: https://orcid.org/0000-0002-7229-5595)
- Megan T. Baldridge (ORCID: https://orcid.org/0000-0002-7030-6131)
- Thomas C. A. Hitch (ORCID: https://orcid.org/0000-0003-2244-7412)
- Naseer Sangwan (ORCID: https://orcid.org/0000-0002-2407-769X)
- Yi Han
Institutions
- Cleveland Clinic (US)
- Washington University in St. Louis (US)
- Cleveland Clinic Lerner College of Medicine (US)
- Universitätsklinikum Aachen (DE)
- RWTH Aachen University (DE)
Publication Details
- Journal
- Science
- Published
- 2024-09-26
- DOI
- https://doi.org/10.1126/science.adk2536
- Citations
- 24
- Primary Topic
- Clostridium difficile and Clostridium perfringens research
- Type
- article
- Field-Weighted Citation Impact
- 9.34
Funders
- Deutsche Forschungsgemeinschaft
- National Institutes of Health