Pathogenesis and Immunobiology of Brucellosis: Review of Brucella -Host Interactions

This review of Brucella- host interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat brucellosis. Brucella spp., as animal pathogens, cause human brucellosis, a zoonosis resulting in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, no patient-friendly treatments or approved human vaccines have been reported. lymphoreticular and reproductive systems with an intracellular lifestyle that limits exposure to innate and adaptive immune responses, sequesters the organism from the effects of antibiotics, and drives clinical disease manifestations and pathology. Stealthy brucellae exploit strategies to establish infection, including: i) evasion of intracellular destruction by restricting fusion of type IV secretion system-dependent Brucella -containing vacuoles with lysosomal compartments, ii) inhibition of apoptosis of infected mononuclear cells, and iii) prevention of dendritic cell maturation, antigen presentation, and activation of naïve T cells, pathogenesis lessons that may be informative for other intracellular pathogens. effector and of the advantage of providing a natural booster response . This approach uses a vaccine depot from which the attenuated Brucella is gradually released over a thirty-day period, and significantly enhances immune protection using highly attenuated LAVs to improve both efficacy and safety 96 . Additionally, recent cell biology findings have revealed the dependence of Brucella infection on the UPR, specifically IRE1α 20, 37 . This dependence may be exploited in an effort to provide LAVs that provide enhanced immune protection. ER stress and TLR-signaling provide a synergistic stimulation of the proinflammatory response 97 . The key to an optimal LAV development strategy is to identify vaccine candidates that fail to restrict the innate immune response, and as a result induce an effective adaptive immune response without safety or reversion concerns.