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NKR-P1B expression in gut-associated innate lymphoid cells is required for the control of gastrointestinal tract infections

Cellular & Molecular Immunology volume 16, pages 868–877 (2019)Cite this article

Abstract

Helper-type innate lymphoid cells (ILC) play an important role in intestinal homeostasis. Members of the NKR-P1 gene family are expressed in various innate immune cells, including natural killer (NK) cells, and their cognate Clr ligand family members are expressed in various specialized tissues, including the intestinal epithelium, where they may play an important role in mucosal-associated innate immune responses. In this study, we show that the inhibitory NKR-P1B receptor, but not the Ly49 receptor, is expressed in gut-resident NK cells, ILC, and a subset of γδT cells in a tissue-specific manner. ILC3 cells constitute the predominant cell subset expressing NKR-P1B in the gut lamina propria. The known NKR-P1B ligand Clr-b is broadly expressed in gut-associated cells of hematopoietic origin. The genetic deletion of NKR-P1B results in a higher frequency and number of ILC3 and γδT cells in the gut lamina propria. However, the function of gut-resident ILC3, NK, and γδT cells in NKR-P1B-deficient mice is impaired during gastrointestinal tract infection by Citrobacter rodentium or Salmonella typhimurium, resulting in increased systemic bacterial dissemination in NKR-P1B-deficient mice. Our findings highlight the role of the NKR-P1B:Clr-b recognition system in the modulation of intestinal innate immune cell functions.

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Acknowledgements

We thank Drs. Vicky Kartsogiannis and Matthew T. Gillespie (Monash Medical Centre, Clayton, VIC, Australia) for providing the Clr-b-deficient (Ocil–/–) mice, Dr. Koho Iizuka (University of Minnesota, Minneapolis, MN, USA) for providing the anti-NKR-P1B (2D12) hybridoma, and Dr. Subash Sad (University of Ottawa, Ottawa, Canada) for providing S. typhimurium bacterium. We further thank Drs. Philpott and Banks (University of Toronto) at the germ-free core facility for providing germ-free animals. This work was supported by Operating Grants from the Canadian Institutes of Health Research (CIHR 86630 to A.P.M. and J.R.C. and CIHR 388337 to A.M.).

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Authors and Affiliations

  1. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada

    Elias Abou-Samra, Zachary Hickey, Ahmad Bakur Mahmoud, Megan M. Tu & Jeffrey Francispillai

  2. Department of Immunology, University of Toronto, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada

    Oscar A. Aguilar, Arthur Mortha & James R. Carlyle

  3. Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    Oscar A. Aguilar & James R. Carlyle

  4. Department of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS, B3H 4R2, Canada

    Michal Scur, Mir Munir A. Rahim & Andrew P. Makrigiannis

  5. College of Applied Medical Sciences, Taibah University, Madinah Munawwarah, Saudi Arabia

    Ahmad Bakur Mahmoud

  6. Division of Anatomical Pathology, Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, 501 Smyth Road, Ottawa, ON, K1H 8L6, Canada

    Sergey Pyatibrat

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Contributions

E.A.-S., Z.H., J.F., O.A.A., M.S., A.B.M., M.M.T., S.P., A.M., and M.M.A.R. performed the experiments and analyzed the data. E.A.-S., J.R.C., A.M., M.M.A.R., and A.P.M. designed the experiments, analyzed the data, and wrote the manuscript. A.P.M. supervised the study.

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Correspondence to Mir Munir A. Rahim or Andrew P. Makrigiannis.

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Abou-Samra, E., Hickey, Z., Aguilar, O.A. et al. NKR-P1B expression in gut-associated innate lymphoid cells is required for the control of gastrointestinal tract infections. Cell Mol Immunol 16, 868–877 (2019). https://doi.org/10.1038/s41423-018-0169-x

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