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Gut Microbiota Promote Hematopoiesis to Control Bacterial Infection

Khosravi, Arya and Yáñez, Alberto and Price, Jeremy G. and Chow, Andrew and Merad, Miriam and Goodridge, Helen S. and Mazmanian, Sarkis K. (2014) Gut Microbiota Promote Hematopoiesis to Control Bacterial Infection. Cell Host & Microbe, 15 (3). pp. 374-381. ISSN 1931-3128. PMCID PMC4144825. doi:10.1016/j.chom.2014.02.006.

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The commensal microbiota impacts specific immune cell populations and their functions at peripheral sites, such as gut mucosal tissues. However, it remains unknown whether gut microbiota control immunity through regulation of hematopoiesis at primary immune sites. We reveal that germ-free mice display reduced proportions and differentiation potential of specific myeloid cell progenitors of both yolk sac and bone marrow origin. Homeostatic innate immune defects may lead to impaired early responses to pathogens. Indeed, following systemic infection with Listeria monocytogenes, germ-free and oral-antibiotic-treated mice display increased pathogen burden and acute death. Recolonization of germ-free mice with a complex microbiota restores defects in myelopoiesis and resistance to Listeria. These findings reveal that gut bacteria direct innate immune cell development via promoting hematopoiesis, contributing to our appreciation of the deep evolutionary connection between mammals and their microbiota.

Item Type:Article
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URLURL TypeDescription CentralArticle
Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2014 Elsevier Inc. Received: September 25, 2013. Revised: December 23, 2013. Accepted: February 19, 2014. Published: March 12, 2014. We thank H. Chu, Y.K. Lee, G. Sharon, A. Nanz (Caltech), and N. Hassanzadeh-Kiabi (Cedars-Sinai) for technical assistance; T. Thron for animal care; and S. McBride, D. Majumdar, S. Damle, P. Mehrabian (Caltech), and members of the Mazmanian laboratory for critical reading of the manuscript. We thank U. Sonnenborn (Ardeypharm GmbH) for the generous gift of Escherichia coli Nissle 1917. A.K. was supported by a predoctoral training grant from the National Institute of Health (GM007616). This research was supported by a Burroughs Wellcome Fund in the Pathogenesis of Infectious Disease award to S.K.M. Author Contributions: A.K., M.M., H.S.G., and S.K.M. designed the research. A.K., A.Y., J.G.P., and A.C. carried out the experiments. A.K., M.M., H.S.G., and S.K.M. wrote the manuscript.
Funding AgencyGrant Number
NIH Predoctoral Training GrantGM007616
Burroughs Wellcome FundUNSPECIFIED
Issue or Number:3
PubMed Central ID:PMC4144825
Record Number:CaltechAUTHORS:20140320-132604670
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Official Citation:Arya Khosravi, Alberto Yáñez, Jeremy G. Price, Andrew Chow, Miriam Merad, Helen S. Goodridge, Sarkis K. Mazmanian, Gut Microbiota Promote Hematopoiesis to Control Bacterial Infection, Cell Host & Microbe, Volume 15, Issue 3, 12 March 2014, Pages 374-381, ISSN 1931-3128, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:44413
Deposited By: Ruth Sustaita
Deposited On:20 Mar 2014 20:51
Last Modified:10 Nov 2021 16:51

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