Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA; Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota Medical School - Twin Cities, Minneapolis, MN 55455, USA.
Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
Immunity. 2014 Feb 20;40(2):213-24. doi: 10.1016/j.immuni.2013.12.013. Epub 2014 Feb 6.
T cell effector functions can be elicited by noncognate stimuli, but the mechanism and contribution of this pathway to the resolution of intracellular macrophage infections have not been defined. Here, we show that CD4(+) T helper 1 (Th1) cells could be rapidly stimulated by microbe-associated molecular patterns during active infection with Salmonella or Chlamydia. Further, maximal stimulation of Th1 cells by lipopolysaccharide (LPS) did not require T-cell-intrinsic expression of toll-like receptor 4 (TLR4), interleukin-1 receptor (IL-1R), or interferon-γ receptor (IFN-γR) but instead required IL-18R, IL-33R, and adaptor protein MyD88. Innate stimulation of Th1 cells also required host expression of TLR4 and inflammasome components that together increased serum concentrations of IL-18. Finally, the elimination of noncognate Th1 cell stimulation hindered the resolution of primary Salmonella infection. Thus, the in vivo bactericidal capacity of Th1 cells is regulated by the response to noncognate stimuli elicited by multiple innate immune receptors.
T 细胞效应功能可被非特异性刺激物诱导，但该途径对细胞内巨噬细胞感染的解决的机制和贡献尚未确定。在这里，我们表明，在沙门氏菌或衣原体的活性感染期间，CD4(+)辅助性 T 细胞 1 (Th1)细胞可被微生物相关分子模式迅速刺激。此外，脂多糖 (LPS) 对 Th1 细胞的最大刺激作用并不需要 TLR4、IL-1R 或 IFN-γR 的 T 细胞内在表达，而是需要 IL-18R、IL-33R 和衔接蛋白 MyD88。Th1 细胞的先天刺激还需要宿主 TLR4 和炎性小体成分的表达，这些成分共同增加了血清中 IL-18 的浓度。最后，消除非特异性 Th1 细胞刺激会阻碍原发性沙门氏菌感染的解决。因此，Th1 细胞的体内杀菌能力受多种先天免疫受体诱导的非特异性刺激反应的调节。
