Submitted to: Innate Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/26/2013
Publication Date: 3/14/2014
Citation: Knetter, S.M., Bearson, S.M., Huang, T., Kurkiewicz, D., Schroyen, M., Nettleton, D., Berman, D.J., Cohen, V., Lunney, J.K., Ramer-Tait, A.E., Wannemuehler, M.J., Tuggle, C.K. 2014. Salmonella enterica serovar Typhimurium-infected pigs with different shedding levels exhibit distinct clinical, peripheral cytokine and transcriptomic immune response phenotypes. Innate Immunity. 21(3):227-241. Interpretive Summary: Salmonella contamination of the environment and during meat processing can occur by pigs that shed the human pathogen in their feces; thus, identifying pigs that shed no or low levels of Salmonella is a desirable trait. A comparison was conducted between two phenotypic populations of pigs inoculated with the same dose of Salmonella enterica serovar Typhimurium: pigs that shed low levels of Salmonella and pigs that persistently shed Salmonella. In response to Salmonella, these two pig populations differed in their clinical profiles, circulating immune cytokine levels, and gene expression patterns. Together, these data suggest that distinct, alternative immune responses to Salmonella Typhimurium infection could result in different shedding outcomes in swine. Understanding these differing response mechanisms to Salmonella infection is critical to maximizing livestock production, enhancing food safety and protecting human health.
Technical Abstract: Foodborne salmonellosis costs the U.S. $2.7 billion each year, including $100 million in annual losses to pork producers. Pigs colonized with Salmonella are usually asymptomatic with varied severity and duration of fecal shedding. Thus, understanding responses that result in less shedding and transmission may provide a mechanism for control early in infection. Fifty-four crossbred pigs were inoculated with Salmonella enterica serovar Typhimurium (ST) and clinical signs, fecal ST shedding, growth performance, peripheral cytokines and whole blood gene expression were measured to characterize the global immune response. The results demonstrated that persistently shedding (PS) pigs had longer pyrexia and elevated serum IL-1beta, TNF-alpha, and IFN-gamma compared to low shedding (LS) pigs, while LS pigs had brief pyrexia, less shedding that decreased more rapidly, and greater serum CXCL8 than PS pigs. The PS pigs up-regulated genes involved with the STAT1, IFNB1 and IFNG networks on day 2, while up-regulation of genes involved in immune response regulation were detected only in LS pigs. This is the first study to examine host responses to ST infection at a clinical, performance, cytokine, and global transcriptomic level. Results indicate that pigs with different shedding outcomes develop distinct immune responses within the first two days after ST infection, and elucidate alternative immune mechanisms that could be targeted to reduce Salmonella shedding and spread.