Transcriptional response of blood leukocytes from turkeys challenged with Salmonella enterica serovar Typhimurium UK1

Authors: MONSON, MELISSA - Iowa State University; Bearson, Bradley - Brad; Sylte, Matthew; Looft, Torey; LAMONT, SUSAN - Iowa State University; Bearson, Shawn

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/21/2020
Publication Date: 2/1/2021
Citation: Monson, M.S., Bearson, B.L., Sylte, M.J., Looft, T.P., Lamont, S.J., Bearson, S.M. 2021. Transcriptional response of blood leukocytes from turkeys challenged with Salmonella enterica serovar Typhimurium UK1. Veterinary Immunology and Immunopathology. 232. Article 110181. https://doi.org/10.1016/j.vetimm.2020.110181.
DOI: https://doi.org/10.1016/j.vetimm.2020.110181

Interpretive Summary: Salmonella is a leading cause of bacterial foodborne disease, resulting in an estimated 1 million illnesses in the U.S. annually. Poultry is a common source of Salmonella-associated foodborne illness, and approximately six percent of illnesses are attributed to turkey consumption. Limiting colonization of food animals by Salmonella could reduce human foodborne disease, and investigating host-pathogen interactions may expose potential strategies of colonization intervention. A study was performed that evaluated the colonization potential of Salmonella enterica serovar Typhimurium (S. Typhimurium) in turkeys as well as the turkeys' response to Salmonella by measuring gene expression in circulating leukocytes, a component of blood that contains various immune cells. Transcriptional analysis indicated that during acute Salmonella infection in turkeys, circulating leukocytes were activated and had the potential to migrate to tissues and respond to the microbes. The results show that S. Typhimurium efficiently colonized 3-week old turkeys and prompted a robust host transcriptional response without producing clinical disease, illustrating the challenge of understanding sub-clinical Salmonella colonization in turkeys but also providing genes and pathways that could be targeted in new or improved mitigation strategies.

Technical Abstract: Non-typhoidal Salmonella is one of the most common causes of bacterial foodborne disease and consumption of contaminated poultry products, including turkey, is one source of exposure. Minimizing Salmonella colonization of commercial turkeys could decrease the incidence of Salmonella-associated human foodborne illness. Understanding host responses to these bacteria could lead to potential strategies to minimize colonization and reduce food safety risk. In this study, we evaluated bacterial load and blood leukocyte transcriptomic responses of 3-week-old turkeys challenged with the Salmonella enterica serovar Typhimurium (S. Typhimurium) UK1 strain. Turkeys (n equals 8/dose) were inoculated by oral gavage with 108 or 1010 colony forming units (CFU) of S. Typhimurium UK1, and fecal shedding and tissue colonization were measured across multiple days post-inoculation (dpi). Fecal shedding was 1-2 log10 higher in the 1010 CFU group than the 108 CFU group, but both doses effectively colonized the crop, spleen, ileum, cecum, colon, bursa of Fabricius and cloaca without causing any detectable clinical signs in either group of birds. Blood leukocytes were isolated from a subset of the birds (n equals 3-4/dpi) both pre-inoculation (0 dpi) and 2 dpi with 1010 CFU and their transcriptomic responses assayed by RNA-sequencing (RNA-seq). At 2 dpi, 647 genes had significant differential expression (DE), including large increases in expression of immune genes such as CCAH221, IL4I1, LYZ, IL13RA2, IL22RA2, and ACOD1. IL1Beta was predicted as a major regulator of DE in the leukocytes, which was predicted to activate cell migration, phagocytosis and proliferation, and to impact the STAT3 and toll-like receptor pathways. These data revealed genes and pathways by which turkey blood leukocytes responded to the pathogen and can provide potential targets for developing intervention strategies or diagnostic assays to mitigate S. Typhimurium colonization in turkeys.