Breed-specific innate immune responses to Brucella abortus strain RB51 and Bacillus Calmette-Guérin in cattle

Bovine brucellosis and bovine tuberculosis are chronic diseases that cause economic and animal health concerns in the global beef and dairy industries due to production losses. The etiologic agents of these diseases, Brucella abortus and Mycobacterium bovis, are intracellular, zoonotic bacterial pathogens that pose a risk to human health. Brucella abortus strain RB51 (RB51) and Bacillus Calmette-Guérin (BCG) are live attenuated vaccines for bovine brucellosis and tuberculosis, respectively, and are known to reduce incidence of these diseases in cattle. However, recent work has suggested that the genetic background of cattle may influence immune responses to these two vaccines. Control of brucellosis and tuberculosis depends on T helper 1 (Th1) mediated immune responses; however, both RB51 and BCG are intracellular bacteria that predominantly localize in monocytes and macrophages which are responsible for initiating immune responses to disease. This study investigates the difference in responses of Hereford and Holstein monocyte-enriched peripheral blood mononuclear cells infected in vitro with RB51, BCG, and combined RB51 + BCG. Transcriptomic data was collected to conduct a targeted evaluation of differentially expressed genes between cell conditions from Holsteins and Herefords related to innate immune responses against intracellular bacteria and the downstream generation of adaptive immune responses. Additionally, breed-specific differences in the production of pro-inflammatory, anti-inflammatory, and Th1-related cytokines by infected monocyte-enriched cells were evaluated. After 16 h of infection with RB51, BCG, or RB51 + BCG, monocyte-enriched cells from Holsteins displayed a transcriptomic profile consistent with enhanced pro-inflammatory and Th1-polarizing responses compared to infected cells from Herefords. Further, Holstein cells also produced significantly higher amounts of Th1-polarizing cytokine than Hereford cells after 72 h of intracellular infection. The breed-specific differences in cellular responses presented here following in vitro infection with RB51, BCG, and RB51 + BCG provide evidence that Hereford and Holstein cattle may develop variable immune responses in vivo to these two vaccines. Results of this study suggest that vaccine efficacy may be influenced by cattle host genetic background within the same species and thus warrants consideration when optimizing vaccination strategies.