Pathogenesis and immunobiology of brucellosis : review of brucella-host interactions

This review of Brucellaehost 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 that results in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, and no patient-friendly treatments or approved human vaccines are reported. Brucellae display strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifestyle that limitsn 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 systemdependent 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 naive T cells, pathogenesis lessons that may be informative for other intracellular pathogens. Data sets of next-generation sequences of Brucella and host time-series global expression fused with proteomics and metabolomics data from in vitro and in vivo experiments now inform interactive cellular pathways and gene regulatory networks enabling full-scale systems biology analysis. The newly identified effector proteins of Brucella may represent targets for improved, safer brucellosis vaccines and therapeutics.Instituto de PatobiologíaFil: de Figueiredo, Paul. Texas A&M University. Department of Veterinary Pathobiology; Estados UnidosFil: de Figueiredo, Paul. Texas AgriLife Research; Estados UnidosFil: de Figueiredo, Paul. Texas A&M University. Norman Borlaug Center; Estados UnidosFil: de Figueiredo, Paul. Texas A&M Health Science Center. Department of Microbial Pathogenesis and Immunology; Estados UnidosFil: Ficht, Thomas A. Texas A&M University. College of Veterinary Medicine & Biomedical Sciences. Department of Veterinary Pathobiology; Estados UnidosFil: Rice-Ficht, Allison C. Texas A&M University. College of Medicine. Department of Molecular and Cellular Medicine; Estados UnidosFil: Rossetti, Carlos Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Adams, Leslie G. Texas A&M University. College of Veterinary Medicine & Biomedical Sciences. Department of Veterinary Pathobiology; Estados Unido