Pulmonary Th17 antifungal immunity is regulated by the gut microbiome

Jeremy P. McAleer, Nikki L H Nguyen, Kong Chen, Pawan Kumar, David M. Ricks, Matthew Binnie, Rachel A. Armentrout, Derek A. Pociask, Aaron Hein, Amy Yu, Amit Vikram, Kyle Bibby, Yoshinori Umesaki, Amariliz Rivera, Dean Sheppard, Wenjun Ouyang, Lora V. Hooper, Jay K. Kolls

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42 Scopus citations

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 RegIIIg, an IL-22-inducible antimicrobial protein with specificity for Gram-positive bacteria. Following infection, increased accumulation of Th17 cells in the lungs of RegIIIg-/- and Il22-/- mice was associated with intestinal segmented filamentous bacteria (SFB) colonization. Although gastrointestinal delivery of rRegIIIg 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.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
JournalJournal of Immunology
Volume197
Issue number1
DOIs
StatePublished - Jul 1 2016

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

McAleer, J. P., Nguyen, N. L. H., Chen, K., Kumar, P., Ricks, D. M., Binnie, M., Armentrout, R. A., Pociask, D. A., Hein, A., Yu, A., Vikram, A., Bibby, K., Umesaki, Y., Rivera, A., Sheppard, D., Ouyang, W., Hooper, L. V., & Kolls, J. K. (2016). Pulmonary Th17 antifungal immunity is regulated by the gut microbiome. Journal of Immunology, 197(1), 97-107. https://doi.org/10.4049/jimmunol.1502566