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Chicken-Specific Kinome Array Reveals that Salmonella enterica Serovar Enteritidis Modulates Host Immune Signaling Pathways in the Cecum to Establish a Persistence Infection
- Michael H. Kogut, Christina L. Swaggerty, James Allen Byrd, Ramesh Selvaraj, Ryan J. Arsenault
- International journal of molecular sciences 2016 v.17 no.8 pp. 1207-1227
- Salmonella Enteritidis, T-lymphocytes, animal disease models, anti-infective agents, bacterial shedding, cecum, chickens, chronic diseases, dephosphorylation, disease resistance, gene expression, host-pathogen relationships, hosts, immunomodulators, inflammation, interferon-gamma, messenger RNA, non-specific protein-tyrosine kinase, phenotype, reverse transcriptase polymerase chain reaction, signal transduction, transcription factor NF-kappa B
- Non-typhoidal Salmonella enterica induce an early, short-lived, pro-inflammatory response in chickens that is asymptomatic of clinical disease and results in a persistent colonization of the gastrointestinal (GI) tract that transmits infections to naïve hosts via fecal shedding of bacteria. The underlying mechanisms that control this persistent colonization of the ceca of chickens by Salmonella are only beginning to be elucidated. We hypothesize that alteration of host signaling pathways mediate the induction of a tolerance response. Using chicken-specific kinomic immune peptide arrays and quantitative RT-PCR of infected cecal tissue, we have previously evaluated the development of disease tolerance in chickens infected with Salmonella enterica serovar Enteritidis (S. Enteritidis) in a persistent infection model (4-14 days post infection). Here, we have further outlined the induction of a tolerance defense strategy in the cecum of chickens infected with S. Enteritidis beginning around 4 days post-primary infection. The response is characterized by alterations in the activation of T cell signaling mediated by the dephosphorylation of phospholipase (c-γ1 [PLCG1]) that inhibits NF-κB signaling and activates NFAT signaling and blockage of interferon-γ (IFN-γ) production through the disruption of the JAK-STAT signaling pathway (dephosphorylation of JAK2, JAK3, and STAT4). Further, we measured a significant down-regulation reduction in IFN-γ mRNA expression. These studies, combined with our previous findings, describe global phenotypic changes in the avian cecum of Salmonella Enteritidis infected chickens that decreases the host responsiveness, resulting in the establishment of persistent colonization. The identified tissue protein kinases also represent potential targets for future antimicrobial compounds for decreasing Salmonella loads in the intestines of food animals before going to market.