BCG Induces Protection against Mycobacterium tuberculosis Infection in the Wistar Rat Model

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.

Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis

“…Guinea pigs were first used for mycobacterial infection studies as a very useful animal model for lymphocyte proliferation assays, and for evaluating dermal reactivity, new TB vaccine candidates, and the capacity of animal model has been widely used in evaluating vaccine-or drug-induced resistance [22,23], for determining anaerobic drug activity [90], estimating the e cacy of BCG vaccination [91], and discovering new TB drugs [21]. Previous studies have indicated that granulomatous lesions (which lack central necrosis) could be observed in the lungs, spleens, lymph nodes, and livers of M. tuberculosis-infected American cotton rats, Lewis rats, Wistar rats, and Sprague-Dawley rats [21,[24][25][26].…”

Effectiveness of the Bacillus Calmette-Guerin vaccine in an Indonesian population with D543N NRAMP1 polymorphism

“…A study of animals demonstrated interesting findings; as shown in a rat model, BCG induced immune protection [25]. Furthermore, this protection was profound in early response in mice with genetic susceptibility (the NRAMP1 gene) [26].…”

The current state of animal models and genomic approaches towards identifying and validating molecular determinants ofMycobacterium tuberculosisinfection and tuberculosis disease

“…2010; Cardona et al . 2011; Singhal et al . 2011) and diabetic rat strains (Sugawara, Yamada and Mizuno 2004b; Sugawara and Mizuno 2008) have been used to develop the rat model of TB infection.…”

“…They have also been used to demonstrate Th1-shifts in immunity following BCG vaccination (Cardona et al . 2011). Unlike mice, rats have been found to form well-organized granulomas and accumulate foamy macrophages (Figure 1), which have been associated with pulmonary lesion resolution (Singhal et al .…”