Natural resistance against brucellosis was reviewed from historical and biological perspectives with regard to animals, humans and Brucella spp. Unfortunately, brucellosis continues to be a serious worldwide bacterial zoonosis of major significance to animal and human populations. Host genetic, innate and adaptive immune factors significantly influence the outcome of brucellosis as does the enabling strategies of intracellular Brucella to evade host factors resulting in a delicate co-evolutionary balance for long term survival for both host and pathogen. Natural (innate) resistance mechanisms include the complex of host cell surface receptors for Brucella pathogen-associated molecular patterns, Toll- IL-1 receptor mediated pathways, factors mediating effective macrophage and dendritic cell maturation and activation, carbohydrate binding proteins, antimicrobial peptides, and inflammatory cytokines orchestrated and regulated by the host genome. Heritability of natural resistance has long been recognized as a complex multigenic trait, however new tools for understanding the genetic basis for innate resistance are now providing a deeper knowledge to identify genes and polymorphisms associated with resistance or susceptibility. Polymorphisms of the 3'UTR of the candidate solute carrier gene, SLC11A1, have been investigated extensively in numerous host species yielding contradictory variable degrees of association with natural resistance to brucellosis in ruminants, and indicating the need for international standardized phenotyping protocols. By coupling new genetic tools with rigorously controlled phenotyping protocols, it is anticipated that applying genetic selection as an additional approach to controlling infectious diseases, such as brucellosis, in domestic animals will become increasingly feasible in future.
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