title: Mechanisms of delayed anti-tuberculosis protection in the lung of parenteral BCG-vaccinated hosts: a critical role of airway luminal T cells.
abstract: The immune mechanisms underlying unsatisfactory pulmonary mucosal protection by parenteral Bacillus Calmette-Guérin (BCG) immunization remain poorly understood. We found that parenteral BCG immunization failed to elicit airway luminal T cells (ALT) whereas it induced significant T cells in the lung interstitium. After Mycobacterium tuberculosis (M.tb) challenge, ALT remained missing for 10 days. The lack of ALT correlated with lack of lung protection for 14 days post-M.tb challenge. To further investigate the role of ALT, ALT were elicited in BCG-immunized animals by intranasal inoculation of M.tb culture-filtrate (CF) proteins. Installment of ALT by CF restored protection in the early phases of M.tb infection, which was linked to rapid increases in ALT, but not in lung interstitial T cells. Also, adoptive transfer of T cells to the airway lumen of BCG-immunized animals also accelerated protection. This study thus provides novel evidence that unsatisfactory lung protection by parenteral BCG immunization is due to delayed ALT recruitment after pulmonary M.tb exposure.
authors.affiliation: McMaster Immunology Research Centre, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: C N
authors.initials: CN
authors.lastname: Horvath
authors.forename: C R
authors.initials: CR
authors.lastname: Shaler
authors.forename: M
authors.initials: M
authors.lastname: Jeyanathan
authors.forename: A
authors.initials: A
authors.lastname: Zganiacz
authors.forename: Z
authors.initials: Z
authors.lastname: Xing
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine