Kogut Michael H, Swaggerty Christina L, Byrd James Allen, Selvaraj Ramesh, Arsenault Ryan J
Southern Plains Agricultural Resarch Center, United States Department of Agriculture, Agricultural Research Service, College Station, TX 77845, USA.
Ohio Agricultural Research Center, The Ohio State University, Wooster, OH 44691, USA.
Int J Mol Sci. 2016 Jul 27;17(8):1207. doi: 10.3390/ijms17081207.
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-γ1 (PLCG1) that inhibits NF-κB signaling and activates nuclear factor of activated T-cells (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.
非伤寒型肠炎沙门氏菌在鸡体内引发早期、短暂的促炎反应，该反应无临床疾病症状，导致胃肠道（GI）持续定植，细菌通过粪便排出将感染传播给未感染的宿主。控制沙门氏菌在鸡盲肠持续定植的潜在机制才刚刚开始被阐明。我们假设宿主信号通路的改变介导了耐受反应的诱导。利用鸡特异性激酶组免疫肽阵列和感染盲肠组织的定量逆转录聚合酶链反应（RT-PCR），我们之前在持续感染模型（感染后4 - 14天）中评估了感染肠炎沙门氏菌血清型肠炎亚种（S. Enteritidis）的鸡的疾病耐受发展情况。在此，我们进一步概述了在初次感染后约四天开始感染肠炎沙门氏菌的鸡盲肠中诱导耐受防御策略的情况。该反应的特征是磷脂酶c-γ1（PLCG1）去磷酸化介导的T细胞信号激活改变，这抑制了NF-κB信号并激活了活化T细胞的核因子（NFAT）信号，以及通过破坏JAK-STAT信号通路（JAK2、JAK3和STAT4去磷酸化）阻断干扰素-γ（IFN-γ）的产生。此外，我们测量到IFN-γ mRNA表达显著下调。这些研究与我们之前的发现相结合，描述了感染肠炎沙门氏菌的鸡的禽盲肠中的整体表型变化，这种变化降低了宿主反应性，导致持续定植的建立。所鉴定的组织蛋白激酶也代表了未来抗菌化合物在食用动物上市前降低肠道中沙门氏菌载量的潜在靶点。
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