title: Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis.
abstract: Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRMcells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and TRMcells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4+T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8+T cells displayed prototypical TRMfeatures. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies.
  
  
  
  BCG remains the only licensed vaccine against TB. Parenterally administered BCG has variable efficacy against pulmonary TB, and thus, improved prevention strategies and a more refined understanding of correlates of vaccine protection are required. Induction of memory T cells has been shown to be essential for protective TB vaccines. Mimicking the natural infection route by mucosal vaccination has been known to generate superior protection against TB in animal models; however, the mechanisms of protection have remained elusive. Here we performed an in-depth analysis to dissect the immunological mechanisms associated with superior mucosal protection in the mouse model of TB. We found that mucosal, and not subcutaneous, BCG vaccination generates lung-resident memory T cell populations that confer protection against pulmonary TB. We establish a comprehensive phenotypic characterization of these populations, providing a framework for future vaccine development.
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Carolina
authors.initials: C
authors.lastname: Perdomo
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zedler
authors.affiliation: Department of Medicine, Charité University Hospital, Berlin, Germany.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Lozza
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saikali
authors.affiliation: Department of Infectious Diseases and Pulmonary Medicine, Charité University Hospital, Berlin, Germany.
authors.forename: Leif E
authors.initials: LE
authors.lastname: Sander
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vogelzang
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany kaufmann@mpiib-berlin.mpg.de.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.|Centre for Biosecurity and Tropical Infectious Diseases, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupz
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D019264:Adoptive Transfer; D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007156:Immunologic Memory; D007279:Injections, Subcutaneous; D008168:Lung / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine