Abstract
Commensal microbiota are critical for the development of local immune responses. In this article, we show that gut microbiota can regulate CD4 T cell polarization during pulmonary fungal infections. Vancomycin drinking water significantly decreased lung Th17 cell numbers during acute infection, demonstrating that Gram-positive commensals contribute to systemic inflammation. We next tested a role for RegIIIγ, an IL-22–inducible antimicrobial protein with specificity for Gram-positive bacteria. Following infection, increased accumulation of Th17 cells in the lungs of RegIIIγ−/− and Il22−/− mice was associated with intestinal segmented filamentous bacteria (SFB) colonization. Although gastrointestinal delivery of rRegIIIγ decreased lung inflammatory gene expression and protected Il22−/− mice from weight loss during infection, it had no direct effect on SFB colonization, fungal clearance, or lung Th17 immunity. We further show that vancomycin only decreased lung IL-17 production in mice colonized with SFB. To determine the link between gut microbiota and lung immunity, serum-transfer experiments revealed that IL-1R ligands increase the accumulation of lung Th17 cells. These data suggest that intestinal microbiota, including SFB, can regulate pulmonary adaptive immune responses.
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Footnotes
This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health Award R37-HL079142 (to J.K.K.) and Grant R01 DK070855 (to L.V.H.); J.P.M. was supported in part by Fellowship F32AI096772. L.V.H. also receives support from the Howard Hughes Medical Institute.
The sequences presented in this article have been submitted to the Metagenomics RAST server under accession number 4541676.3.
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- B6
- C57BL/6
- BSS
- balanced salt solution
- DC
- dendritic cell
- GF
- germ-free
- IL-1RA
- IL-1R antagonist
- o.p.
- oropharyngeal
- OTU
- operational taxonomic unit
- SFB
- segmented filamentous bacteria
- siLP
- small intestinal lamina propria
- Treg
- regulatory T cell
- WT
- wild-type.
- Received December 9, 2015.
- Accepted April 25, 2016.
- Copyright © 2016 by The American Association of Immunologists, Inc.