Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection

Maria Carolina Amezcua Vesely; Paris Pallis; Piotr Bielecki; Jun Siong Low; Jun Zhao; Christian C D Harman; Lina Kroehling; Ruaidhrí Jackson; Will Bailis; Paula Licona-Limón; Hao Xu; Norifumi Iijima; Padmini S Pillai; Daniel H Kaplan; Casey T Weaver; Yuval Kluger; Monika S Kowalczyk; Akiko Iwasaki; Joao P Pereira; Enric Esplugues; Nicola Gagliani; Richard A Flavell

doi:10.1016/j.cell.2019.07.032

Effector T_H17 Cells Give Rise to Long-Lived T_RM Cells that Are Essential for an Immediate Response against Bacterial Infection

Cell. 2019 Aug 22;178(5):1176-1188.e15. doi: 10.1016/j.cell.2019.07.032.

Authors

Maria Carolina Amezcua Vesely¹, Paris Pallis², Piotr Bielecki², Jun Siong Low², Jun Zhao³, Christian C D Harman¹, Lina Kroehling², Ruaidhrí Jackson², Will Bailis², Paula Licona-Limón⁴, Hao Xu², Norifumi Iijima², Padmini S Pillai⁵, Daniel H Kaplan⁶, Casey T Weaver⁷, Yuval Kluger⁸, Monika S Kowalczyk⁹, Akiko Iwasaki¹, Joao P Pereira², Enric Esplugues¹⁰, Nicola Gagliani¹¹, Richard A Flavell¹²

Affiliations

¹ Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA.
² Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA.
³ Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA; Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
⁴ Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, México.
⁵ Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA; Koch Institute for Integrative Cancer Research and Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
⁶ Department of Dermatology and Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
⁷ Departments of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁸ Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA; Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA; Applied Mathematics Program, Yale University, New Haven, CT 06511, USA.
⁹ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA; Laboratory of Molecular and Cellular Immunology, Principe Felipe Research Center (CIPF), 46012 Valencia, Spain.
¹¹ Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA; I. Medical Department and Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf 20246 Hamburg, Germany; Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, 17176 Stockholm, Sweden. Electronic address: n.gagliani@uke.de.
¹² Department of Immunobiology, School of Medicine, Yale University, New Haven, CT, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA. Electronic address: richard.flavell@yale.edu.

Abstract

Adaptive immunity provides life-long protection by generating central and effector memory T cells and the most recently described tissue resident memory T (T_RM) cells. However, the cellular origin of CD4 T_RM cells and their contribution to host defense remain elusive. Using IL-17A tracking-fate mouse models, we found that a significant fraction of lung CD4 T_RM cells derive from IL-17A-producing effector (T_H17) cells following immunization with heat-killed Klebsiella pneumonia (Kp). These exT_H17 T_RM cells are maintained in the lung by IL-7, produced by lymphatic endothelial cells. During a memory response, neither antibodies, γδ T cells, nor circulatory T cells are sufficient for the rapid host defense required to eliminate Kp. Conversely, using parabiosis and depletion studies, we demonstrated that exT_H17 T_RM cells play an important role in bacterial clearance. Thus, we delineate the origin and function of airway CD4 T_RM cells during bacterial infection, offering novel strategies for targeted vaccine design.

Keywords: Fate mapping; IL-17; IL-7; T(H)17; Tissue resident memory CD4 T cells; exT(H)17.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD4-Positive T-Lymphocytes / cytology
CD4-Positive T-Lymphocytes / immunology
CD4-Positive T-Lymphocytes / metabolism
Diphtheria Toxin / pharmacology
Disease Models, Animal
Female
Immunologic Memory
Interleukin-17 / genetics
Interleukin-17 / metabolism
Klebsiella Infections / immunology*
Klebsiella Infections / pathology
Klebsiella pneumoniae / immunology
Klebsiella pneumoniae / pathogenicity
Lung / drug effects
Lung / metabolism
Lung / microbiology
Mice
Mice, Inbred C57BL
Th17 Cells / cytology
Th17 Cells / immunology*
Th17 Cells / metabolism

Substances

Diphtheria Toxin
Interleukin-17

Abstract

Publication types

MeSH terms

Substances

Grants and funding