Centre for Immunology and Infection Control and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Scand J Immunol. 2023 May;97(5):e13263. doi: 10.1111/sji.13263. Epub 2023 Mar 15.
Urogenital chlamydial infections continue to increase with over 127 million people affected annually, causing significant economic and public health pressures. While the role of traditional MHCI and II peptide presentation is well defined in chlamydial infections, the role of lipid antigens in immunity remains unclear. Natural killer (NK) T cells are important effector cells that recognize and respond to lipid antigens during infections. Chlamydial infection of antigen-presenting cells facilitates presentation of lipid on the MHCI-like protein, CD1d, which stimulates NKT cells to respond. During urogenital chlamydial infection, wild-type (WT) female mice had significantly greater chlamydial burden than CD1d (NKT-deficient) mice, and had significantly greater incidence and severity of immunopathology in both primary and secondary infections. WT mice had similar vaginal lymphocytic infiltrate, but 59% more oviduct occlusion compared to CD1d mice. Transcriptional array analysis of oviducts day 6 post-infection revealed WT mice had elevated levels of Ifnγ (6-fold), Tnfα (38-fold), Il6 (2.5-fold), Il1β (3-fold) and Il17a (6-fold) mRNA compared to CD1d mice. In infected females, oviduct tissues had an elevated infiltration of CD4 -invariant NKT (iNKT) cells, however, iNKT-deficient Jα18 mice had no significant differences in hydrosalpinx severity or incidence compared to WT controls. Lipid mass spectrometry of surface-cleaved CD1d in infected macrophages revealed an enhancement of presented lipids and cellular sequestration of sphingomyelin. Taken together, these data suggest an immunopathogenic role for non-invariant NKT cells in urogenital chlamydial infections, facilitated by lipid presentation via CD1d via infected antigen-presenting cells.
泌尿生殖道沙眼衣原体感染持续增加，每年受影响的人数超过 1.27 亿，给经济和公共卫生带来巨大压力。虽然传统的 MHCI 和 II 肽呈递在沙眼衣原体感染中作用明确，但脂质抗原在免疫中的作用仍不清楚。自然杀伤 (NK) T 细胞是在感染过程中识别和响应脂质抗原的重要效应细胞。衣原体感染抗原呈递细胞促进脂质在 MHCI 样蛋白 CD1d 上的呈递，刺激 NKT 细胞作出反应。在泌尿生殖道沙眼衣原体感染中，野生型 (WT) 雌性小鼠的衣原体负荷明显高于 CD1d (NKT 缺陷) 小鼠，在初次和再次感染中均有更高的发病率和更严重的免疫病理学。WT 小鼠的阴道淋巴细胞浸润相似，但与 CD1d 小鼠相比，输卵管阻塞的比例高 59%。感染后第 6 天对输卵管进行转录组分析显示，WT 小鼠的 Ifnγ (6 倍)、Tnfα (38 倍)、Il6 (2.5 倍)、Il1β (3 倍) 和 Il17a (6 倍) mRNA 水平明显高于 CD1d 小鼠。在感染的雌性中，输卵管组织中有较高水平的 CD4 不变 NKT (iNKT) 细胞浸润，但 iNKT 缺陷 Jα18 小鼠与 WT 对照相比，在积水的严重程度或发生率上没有显著差异。感染巨噬细胞表面切割的 CD1d 的脂质质谱分析显示呈递的脂质增强和鞘磷脂的细胞隔离。综上所述，这些数据表明非不变 NKT 细胞在泌尿生殖道沙眼衣原体感染中具有免疫病理作用，这是通过感染的抗原呈递细胞通过 CD1d 呈递脂质所促进的。
