College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China; Faculty of Veterinary Medicine, Sumy National Agrarian University, Sumy 40021, Ukraine.
College of Animal Science and Veterinary Medicine, Henan Institute of Science and Technology, Xinxiang 453003, China.
Vet Microbiol. 2023 Sep;284:109817. doi: 10.1016/j.vetmic.2023.109817. Epub 2023 Jun 17.
Salmonella enterica serovar Pullorum (S. Pullorum) can regulate host immunity via special effectors that promote persistent infection and its intracellular survival. SteE as an anti-inflammatory effector is involved in the systemic infection of Salmonella in host macrophages. Macrophage activation can indirectly reflect the immune regulatory function of T helper type 1 (Th1)/T helper type 2 (Th2) cytokines. However, information concerning the regulation of Th1/Th2 cytokine expression by steE in S. Pullorum infection is limited. This study evaluates the effects of steE on the Th1/Th2 balance, STAT3/SOCS3 pathway, and NF-κB P65 activation in S. Pullorum-infected HD-11 cells and in chicken models. We demonstrated that steE diminished the expression of Th1-related cytokines (IFN-γ and IL-12) and promoted the expression of Th2-related cytokines (IL-4 and IL-10) in HD-11 cells and chicken models of S. Pullorum infection. SOCS3 silencing suppressed the function of steE in HD-11 cells and led to the imbalance of Th1/Th2-related cytokines. SteE promoted SOCS3 expression by activating STAT3 in HD-11 cells. Moreover, steE inhibited NF-κB P65 expression and blocked its translocation to the nucleus by promoting SOCS3 expression. Our results illustrated that steE regulated the expression of Th1/Th2 cytokines via modulation of the STAT3/SOCS3 and NF-κB axis, which might be associated with Th1/Th2 cell differentiation and could, therefore, be a novel therapeutic strategy against salmonellosis.
肠炎沙门氏菌血清 Pullorum（S. Pullorum）可以通过促进持续感染和细胞内存活的特殊效应子来调节宿主免疫。SteE 作为一种抗炎效应子，参与沙门氏菌在宿主巨噬细胞中的系统性感染。巨噬细胞的激活可以间接反映辅助性 T 细胞 1（Th1）/辅助性 T 细胞 2（Th2）细胞因子的免疫调节功能。然而，关于 steE 在 S. Pullorum 感染中对 Th1/Th2 细胞因子表达的调节信息有限。本研究评估了 steE 对 S. Pullorum 感染的 HD-11 细胞和鸡模型中 Th1/Th2 平衡、STAT3/SOCS3 途径和 NF-κB P65 激活的影响。我们表明，steE 在 HD-11 细胞和鸡 S. Pullorum 感染模型中降低了 Th1 相关细胞因子（IFN-γ 和 IL-12）的表达，并促进了 Th2 相关细胞因子（IL-4 和 IL-10）的表达。SOCS3 沉默抑制了 steE 在 HD-11 细胞中的功能，并导致 Th1/Th2 相关细胞因子失衡。SteE 通过激活 STAT3 在 HD-11 细胞中促进 SOCS3 的表达。此外，steE 通过促进 SOCS3 的表达抑制 NF-κB P65 的表达并阻止其向核内易位。我们的结果表明，steE 通过调节 STAT3/SOCS3 和 NF-κB 轴来调节 Th1/Th2 细胞因子的表达，这可能与 Th1/Th2 细胞分化有关，因此可能是治疗沙门氏菌病的一种新策略。
