Pathogenesis of Brucella

The goal of this chapter is to describe the pathogenesis of Brucella reporting, the host-pathogen and the cell/macrophage Brucella interactions, and the major virulence factors of this bacteria genus. The epithelium of the respiratory, digestive and reproductive tracts are the most important ports of bacterium entry in the host. The mechanisms by which Brucella enters the cells and evades the host immune system remains poorly understood. However, in the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated. Brucella has the ability to survive and replicate intracellularly in mononuclear phagocytes and to control host immune responses. This pathogen developed several strategies to evade the host s immune defense mechanisms preventing inflammatory responses at the site of entrance in the host and maintain the infection. Brucella bacterium is internalized by macrophages and dendritic cells, and invades the bloodstream and lymphatics causing an eventual transitory bacteremia. Inside phagocytic cells, few bacteria can survive. Brucella also shows a strong tissue tropism to monocytes in the liver, spleen, lymph nodes, bone marrow and trophoblasts. All these target cells lead to clinical manifestations, characterized by infection in lymphoid tissues and inflammatory lesions in the reproductive tract of pregnant females. Unlike other bacteria, Brucella lacks classical bacterial virulence factors such as exotoxins, capsules, secreted proteases, fimbriae, flagella, virulence plasmids, resistant strains and phage-encoded toxins. Other virulence factors have been implicated in the pathogenesis as the type IV secretion system, the BvrR/BvrS two component regulatory system, the Brucella intact lipopolysaccharide O-antigen in smooth strains, and cyclic -1,2-glucans. Toll-like receptors are single-pass type I transmembranespanning of proteins that play a key role in the innate immune system. Future perspectives include new genomics and omics technologies and software tools to analyze virulent genes associated with a Brucella infection. This information will provide a better knowledge of infection and Brucella-host relations that are necessary for vaccine production and strategies to prevent and control brucellosis in small ruminants.