Abstract
Brucella abortus is a Gram-negative, facultative intracellular pathogen for several mammals, including humans. Live attenuated B. abortus strain RB51 is currently the official vaccine used against bovine brucellosis in the United States and several other countries. Overexpression of protective B. abortus antigen Cu/Zn superoxide dismutase (SOD) in a recombinant strain of RB51 (strain RB51SOD) significantly increases its vaccine efficacy against virulent B. abortus challenge in a mouse model. An attempt has been made to better understand the mechanism of the enhanced protective immunity of RB51SOD compared to its parent strain RB51. We previously reported that RB51SOD stimulated enhanced Th1 immune response. In this study, we further found that T effector cells derived from RB51SOD-immunized mice exhibited significantly higher cytotoxic T lymphocyte activity than T effector cells derived from RB51-immunized mice against virulent B. abortus-infected target cells. Meanwhile, the macrophage responses to these two strains were also studied. Compared to RB51, RB51SOD cells had a lower survival rate in macrophages and induced lower levels of macrophage apoptosis and necrosis. The decreased survival of RB51SOD cells correlates with the higher sensitivity of RB51SOD, compared to RB51, to the bactericidal action of either Polymyxin B or sodium dodecyl sulfate (SDS). Furthermore, a physical damage to the outer membrane of RB51SOD was observed by electron microscopy. Possibly due to the physical damage, overexpressed Cu/Zn SOD in RB51SOD was found to be released into the bacterial cell culture medium. Therefore, the stronger adaptive immunity induced by RB51SOD did not correlate with the low level of innate immunity induced by RB51SOD compared to RB51. This unique and apparently contradictory profile is likely associated with the differences in outer membrane integrity and Cu/Zn SOD release.
Highlights
Brucella abortus is a Gram-negative, facultative intracellular bacterium that causes brucellosis in humans and many animals (Corbel, 1997)
We further found that T effector cells derived from RB51SOD-immunized mice exhibited significantly higher cytotoxic T lymphocyte activity thanT effector cells derived from RB51-immunized mice against virulent B. abortus-infected target cells
We initially demonstrated that RB51SOD induces a higher cytotoxic T lymphocyte (CTL) activity against virulent Brucella infection in vaccinated mice than RB51, which explains the enhanced protection induced by RB51SOD
Summary
Brucella abortus is a Gram-negative, facultative intracellular bacterium that causes brucellosis in humans and many animals (Corbel, 1997). Brucellosis is one of the most common zoonotic diseases. It infects approximately 500,000 humans annually worldwide. The virulence of Brucella relies heavily on their ability to survive and replicate within the vacuolar phagocytic compartments of macrophages (Baldwin and Winter, 1994; Roop et al, 2009). The ability of different species or strains of Brucella to survive in macrophages in vitro correlates with bacterial virulence in vivo. The virulence of Brucella in vivo and their ability to survive in macrophages in vitro correlates inversely with the innate resistance of the host to brucellosis (Baldwin and Winter, 1994). The treatment of Frontiers in Cellular and Infection Microbiology www.frontiersin.org
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