Dichotomous regulation of group 3 innate lymphoid cells by nongastric Helicobacter species

John W. Bostick; Yetao Wang; Zeli Shen; Yong Ge; Jeffrey Brown; Zong-ming E. Chen; Mansour Mohamadzadeh; James G. Fox; Liang Zhou

doi:10.1073/pnas.1908128116

New Research In

Edited by David Artis, Weill Cornell Medical College, New York, NY, and accepted by Editorial Board Member Ruslan Medzhitov October 24, 2019 (received for review May 10, 2019)

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Significance

Innate lymphoid cells (ILCs) in the intestine maintain both defense against pathogens and homeostasis of intestinal tissue, which is exposed to environmental influences, including microbes and ingested foods. We identified a pair of Helicobacter species that activate ILCs but negatively regulate proliferation of group 3 RORγt⁺ ILCs (ILC3s) that are important for host immunity and inflammation. This opens the door for future investigations that explore the molecular factors produced by microbes that may influence the maintenance of ILC3s in the intestine.

Abstract

Intestinal innate lymphoid cells (ILCs) contribute to the protective immunity and homeostasis of the gut, and the microbiota are critically involved in shaping ILC function. However, the role of the gut microbiota in regulating ILC development and maintenance still remains elusive. Here, we identified opposing effects on ILCs by two Helicobacter species, Helicobacter apodemus and Helicobacter typhlonius, isolated from immunocompromised mice. We demonstrated that the introduction of both Helicobacter species activated ILCs and induced gut inflammation; however, these Helicobacter species negatively regulated RORγt⁺ group 3 ILCs (ILC3s), especially T-bet⁺ ILC3s, and diminished their proliferative capacity. Thus, these findings underscore a previously unknown dichotomous regulation of ILC3s by Helicobacter species, and may serve as a model for further investigations to elucidate the host–microbe interactions that critically sustain the maintenance of intestinal ILC3s.

Footnotes

↵¹Present address: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655.
↵²To whom correspondence may be addressed. Email: liangzhou497{at}ufl.edu.

Author contributions: J.W.B. and L.Z. designed research; J.W.B., Y.W., Z.S., Y.G., Z.-m.E.C., M.M., and J.G.F. performed research; Z.S., J.B., M.M., and J.G.F. contributed new reagents/analytic tools; J.W.B., Z.-m.E.C., and L.Z. analyzed data; and J.W.B. and L.Z. wrote the paper.
The authors declare no competing interest.
This article is a PNAS Direct Submission. D.A. is a guest editor invited by the Editorial Board.
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE136171).
This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1908128116/-/DCSupplemental.

Published under the PNAS license.

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