Chicken-Specific Kinome Array Reveals that Salmonella enterica Serovar Enteritidis Modulates Host Immune Signaling Pathways in the Cecum to Establish a Persistence Infection
Date
2016-07-27
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MDPI
Abstract
Non-typhoidal Salmonella enterica induces 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 an tolerance defense strategy in the cecum of chickens infected with
S. Enteritidis beginning around four 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 nuclear factor of activated T-cells (NFAT)
signaling and blockage of interferon-! (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.
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Citation
Kogut, Michael H., et al. "Chicken-specific kinome array reveals that Salmonella enterica serovar Enteritidis modulates host immune signaling pathways in the cecum to establish a persistence infection." International Journal of Molecular Sciences 17.8 (2016): 1207.