|Kogut, Michael - Mike|
|Swaggerty, Christina - Christi|
|Byrd Ii, James - Allen|
|SELVARAJ, RAMESH - The Ohio State University|
|ARSENAULT, RYAN - University Of Delaware|
Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/8/2016
Publication Date: 7/27/2016
Publication URL: https://handle.nal.usda.gov/10113/5451329
Citation: Kogut, M.H., Swaggerty, C.L., Byrd, J.A., Selvaraj, R., Arsenault, R.J. 2016. Chicken-specific kinome array reveals that Salmonella enterica serovar Enteritidis modulates host immune signaling pathways in the cecum to establish a persistent infection. International Journal of Molecular Sciences. 17(8):1-20.
Interpretive Summary: Baby chicks get infected with Salmonella bacteria early in life, and the bacteria are able to survive in the chicks throughout their life. Because of this, Salmonella can be consistently released from the birds and then infect the other chicks. Also, the presence of these pathogens in the chicks when they go to market means that they can contaminate chicken meat products, and cause food poisoning in humans. The purpose of these experiments is to try to understand how Salmonella can survive in chicks for so long without being "seen" by the chick's immune system. We found that Salmonella causes a change in the immune response of the baby chicks so that they are "invisible" to the immune system. Thus, the immune cells cannot attack this bug and kill it. These results are important to the pharmaceutical industry because we have identified a specific target to stimulate the bird’s immune system and provide protection against infection.
Technical Abstract: 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-'1 [PLCG1]) that inhibits NF-'B signaling and activates NFAT signaling and blockage of interferon-gamma (IFN-') 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-' 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.