Abstract
Our understanding of the correlation of Mycobacterium bovis Bacille Calmette-Guerin (BCG)-mediated immune responses and protection against Mycobacterium tuberculosis (Mtb) infection is still limited. We have recently characterized a Wistar rat model of experimental tuberculosis (TB). In the present study, we evaluated the efficacy of BCG vaccination in this model. Upon Mtb challenge, BCG vaccinated rats controlled growth of the bacilli earlier than unvaccinated rats. Histopathology analysis of infected lungs demonstrated a reduced number of granulomatous lesions and lower parenchymal inflammation in vaccinated animals. Vaccine-mediated protection correlated with the rapid accumulation of antigen specific CD4+ and CD8+ T cells in the infected lungs. Immunohistochemistry further revealed higher number of CD8+ cells in the pulmonary granulomas of vaccinated animals. Evaluation of pulmonary immune responses in vaccinated and Mtb infected rats by real time PCR at day 15 post-challenge showed reduced expression of genes responsible for negative regulation of Th1 immune responses. Thus, early protection observed in BCG vaccinated rats correlated with a similarly timed shift of immunity towards the Th1 type response. Our data support the importance of (i) the Th1-Th2 balance in the control of mycobacterial infection and (ii) the value of the Wistar rats in understanding the biology of TB.
Highlights
Tuberculosis (TB) remains a major challenge to public health world wide, with an estimated 2 million deaths annually and 2.2 billion people infected with latent Mycobacterium tuberculosis (Mtb) across the globe [1]
We have recently shown that the Wistar rats can partially control low dose infection of Mtb and that the extent of control was a function of infecting dose and strain of Mtb used [12]
We examined whether bacille Calmette-Geurin (BCG) vaccination would enhance mycobacterial control in low dose Mtb infected rats
Summary
Tuberculosis (TB) remains a major challenge to public health world wide, with an estimated 2 million deaths annually and 2.2 billion people infected with latent Mycobacterium tuberculosis (Mtb) across the globe [1]. BCG has been shown to be partially protective against active TB [3,4,5] and against the more severe form of disease in young babies [6]. These effects of BCG are due to the induction of cell-mediated immune responses [7]. Analysis of mycobacteriaspecific T cells secreting interferon-gamma (IFN-c) is widely used as an indicator of vaccine efficacy. We still do not fully understand how BCG modulates the immune response, resulting in its protective effect [2,8]
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