iScience (Jul 2022)
Group 3 innate lymphocytes make a distinct contribution to type 17 immunity in bladder defence
- Alexandra M. Riding,
- Kevin W. Loudon,
- Andrew Guo,
- John R. Ferdinand,
- Laurence S.C. Lok,
- Nathan Richoz,
- Andrew Stewart,
- Tomas Castro-Dopico,
- Zewen Kelvin Tuong,
- Remi Fiancette,
- Georgina S. Bowyer,
- Aaron Fleming,
- Eleanor S. Gillman,
- Ondrej Suchanek,
- Krishnaa T. Mahbubani,
- Kourosh Saeb-Parsy,
- David Withers,
- Gordan Dougan,
- Simon Clare,
- Menna R. Clatworthy
Affiliations
- Alexandra M. Riding
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Kevin W. Loudon
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Andrew Guo
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK; Cellular Generics, Wellcome Sanger Institute, Hinxton, UK
- John R. Ferdinand
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Laurence S.C. Lok
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Nathan Richoz
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Andrew Stewart
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Tomas Castro-Dopico
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Zewen Kelvin Tuong
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK; Cellular Generics, Wellcome Sanger Institute, Hinxton, UK
- Remi Fiancette
- Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Georgina S. Bowyer
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Aaron Fleming
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Eleanor S. Gillman
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Ondrej Suchanek
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Krishnaa T. Mahbubani
- University of Cambridge Department of Surgery, Cambridge, UK
- Kourosh Saeb-Parsy
- University of Cambridge Department of Surgery, Cambridge, UK; NIHR Cambridge Biomedical Research Centre, Cambridge, UK; Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK
- David Withers
- Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
- Gordan Dougan
- Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Simon Clare
- Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK
- Menna R. Clatworthy
- Molecular Immunity Unit, University of Cambridge Department of Medicine MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, UK; Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge CB2 0AW, UK; Cellular Generics, Wellcome Sanger Institute, Hinxton, UK; NIHR Cambridge Biomedical Research Centre, Cambridge, UK; Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 7
p. 104660
Abstract
Summary: Bladder infection affects a hundred million people annually, but our understanding of bladder immunity is incomplete. We found type 17 immune response genes among the most up-regulated networks in mouse bladder following uropathogenic Escherichia coli (UPEC) challenge. Intravital imaging revealed submucosal Rorc+ cells responsive to UPEC challenge, and we found increased Il17 and IL22 transcripts in wild-type and Rag2−/− mice, implicating group 3 innate lymphoid cells (ILC3s) as a source of these cytokines. NCR-positive and negative ILC3 subsets were identified in murine and human bladders, with local proliferation increasing IL17-producing ILC3s post infection. ILC3s made a more limited contribution to bladder IL22, with prominent early induction of IL22 evident in Th17 cells. Single-cell RNA sequencing revealed bladder NCR-negative ILC3s as the source of IL17 and identified putative ILC3-myeloid cell interactions, including via lymphotoxin-β-LTBR. Altogether, our data provide important insights into the orchestration and execution of type 17 immunity in bladder defense.
