Mechanisms of delayed anti-tuberculosis protection in the lung of parenteral BCG-vaccinated hosts: a critical role of airway luminal T cells

Mucosal Immunol. 2012 Jul;5(4):420-31. doi: 10.1038/mi.2012.19. Epub 2012 Mar 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Bacterial / immunology
  • BCG Vaccine / immunology*
  • Disease Models, Animal
  • Female
  • Immunologic Memory
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis / immunology
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / microbiology
  • T-Lymphocytes / immunology*
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / prevention & control*

Substances

  • Antigens, Bacterial
  • BCG Vaccine