Molecular and immmunological analyses of cytokines and γδT cells in intracellular infection of Salmonella

摘要人类对沙门氏菌宿主免疫应答的认识尚不充分。在本研究中，Th1-和Th-1包括细胞因子和T细胞反应在沙门氏菌病进行了研究。沙门氏菌病患者急性期血清Th-1和含Th-1的细胞因子水平升高。此外，系统性沙门氏菌病患者血清IL-15和IL-18水平显著高于肠胃炎患者。经连续测定，胃肠炎组血清IFN-γ、IL-12、IL-15、IL-18水平较系统性组更易恢复正常。IFN-γ水平与IL-12、IL-18水平显著相关。此外，IL-15水平与IL-18水平显著相关。此外，IFN-γ、IL-15和IL-18水平与发烧持续时间显著相关。在沙门氏菌体外刺激下，沙门氏菌、卡介苗和大肠杆菌均能产生IL-15和IL-18，而在沙门氏菌体外刺激下，IL-12和IFN-γ优先产生。抗il -12单抗或抗il -18单抗显著抑制沙门氏菌诱导的IFN-γ产生，而抗il - 15单抗无显著抑制作用。HLA-DR+T细胞、CD69+T细胞、γδT细胞和HLA-DR+γδT细胞的系统性升高明显高于对照组。HLA-DR+T细胞数量与血清IFN-γ、IL-15、IL-18水平相关。HLA-DR+γδT细胞数与IL-15水平无显著相关性。综上所述，IL-12、IL-18和IL-15具有复杂的相互作用，可能参与了总T细胞的活化和γδT细胞的扩增，从而产生IFN-，从而保护人类免受沙门氏菌感染。

AbstractKnowledge of the host immune response against Salmonella is not sufficient in humans. In the present study, Th1- and Th-1 including cytokines and T cell response were investigated in salmonellosis.Serum Th-1 and Th-1including cytokine levels at acute phase in patients with salmonellosis were elevated. In addition, serum levels of IL-15 and IL-18 in patients with systematic form of salmonellosis were significantly higher than those in patients gastroenteritis form. By serial determination, serum IFN-γ ,IL-12, IL-15 and IL-18 levels in gastroenteritis form returned to normal levels easier than those in systematic form.IFN-γ level was significantly correlated with IL-12 and IL-18 levels. In addition, IL-15 level was significantly correlated with IL-18 level. Furthermore, IFN-γ , IL-15 and IL-18 levels were significantly correlated with duration with fever.Upon stimulation with Salmonella in vitro, IL-15 and IL-18 were produced by Salmonella, BCG or E. coli stimulation in both salmonellosis and controls, while IL-12 and IFN-γ were preferentially produced upon stimulation with Salmonella in Salmonellosis. A significant inhibition of Salmonella -induced IFN-γ production by anti-IL-12 mAb or anti-IL-18 mAb but not by anti-IL 15 mAb.HLA-DR+T cells, CD69+T cells, γδT cells and HLA-DR+γδT cells were significantly elevated in systematic form than in gastroenteritis from. HLA-DR+T cell-number tended to correlate with serum IFN-γ, IL-15 and IL-18 levels. HLA-DR+γδT cell-number was marginally associated with IL-15 levels. Sorted γδT cells contained significantly higher levels of IFN-γ mRNA than αβT cells both in systemic and gastroenteritis formsIn summary, IL-12, IL-18, and IL-15, with complex mutual interactions , appear to be involved in total T cell activation as well as γδT cell-expansion, resulting in IFN- production for the protection against Salmonella infection in humans.