Igietseme J U, Ananaba G A, Bolier J, Bowers S, Moore T, Belay T, Lyn D, Black C M
Department of Microbiology, Morehouse School of Medicine, Spelman College, Atlanta, GA, USA.
Immunology. 1999 Dec;98(4):510-9. doi: 10.1046/j.1365-2567.1999.00926.x.
Recent studies in animal models of genital chlamydial disease revealed that early recruitment of dendritic cells and specific T helper type-1 (Th1) cells into the genital mucosae is crucial for reducing the severity of the acute phase of a cervico-vaginal infection and arresting ascending disease. These immune effectors are therefore important for preventing major complications of genital chlamydial infection. Other in vitro studies showed that intercellular adhesion molecule-1 (ICAM-1) plays a role in the antichlamydial action of specific CD4+ and CD8+ T cells. In the present study, we investigated the clinicopathological consequences of ICAM-1 deficiency during chlamydial genital infection in ICAM-1 knockout (ICAM-1KO) mice, and analysed the cellular and molecular immunological bases for any observed pathology or complication. Following a primary genital infection of female ICAM-l-/- and ICAM-1+/+ mice, the intensity of the disease during the first 3 weeks (as assessed by shedding of chlamydiae in the genital tract) was significantly greater in ICAM-1KO mice than in ICAM-1+/+ mice (P < 0.0001), although both ICAM-l-/- and ICAM-1+/+ mice subsequently cleared the primary infection. There was greater ascending disease during the initial stage of the infection, and a higher incidence of tubal disease (hydrosalpinx formation) after multiple infections in ICAM-l-/- mice. Analysis of the cellular and molecular bases for the increased acute and ascending disease in ICAM-l-/- mice revealed that the high affinity of ICAM-1 for leucocyte function antigen type-1 is a property that promotes rapid activation of specific Th1 cells, as well as their early recruitment into the genital mucosa. Moreover, ICAM-1 was more important for naive T-cell activation than primed Th1 cells, although its absence delayed or suppressed immune T-cell activation by at least 50%. Taken together, these results indicated that ICAM-1 is crucial for rapid T-cell activation, early recruitment and control of genitally acquired Chlamydia trachomatis.
近期针对生殖道衣原体病动物模型的研究表明，树突状细胞和特定1型辅助性T细胞（Th1）早期募集至生殖黏膜对于减轻宫颈-阴道感染急性期的严重程度以及阻止疾病上行至关重要。因此，这些免疫效应细胞对于预防生殖道衣原体感染的主要并发症很重要。其他体外研究显示，细胞间黏附分子-1（ICAM-1）在特定CD4+和CD8+ T细胞的抗衣原体作用中发挥作用。在本研究中，我们调查了ICAM-1基因敲除（ICAM-1KO）小鼠衣原体生殖道感染期间ICAM-1缺乏的临床病理后果，并分析了任何观察到的病理或并发症的细胞和分子免疫学基础。雌性ICAM-1-/-和ICAM-1+/+小鼠初次生殖道感染后，ICAM-1KO小鼠在最初3周内疾病的严重程度（通过生殖道衣原体脱落评估）显著高于ICAM-1+/+小鼠（P < 0.0001），尽管ICAM-1-/-和ICAM-1+/+小鼠随后均清除了初次感染。在感染初期，ICAM-1-/-小鼠的上行性疾病更严重，多次感染后输卵管疾病（输卵管积水形成）的发生率更高。对ICAM-1-/-小鼠急性和上行性疾病增加的细胞和分子基础分析显示，ICAM-1与白细胞功能抗原1型的高亲和力是促进特定Th1细胞快速活化及其早期募集至生殖黏膜的特性。此外，ICAM-1对初始T细胞活化比已致敏的Th1细胞更重要，尽管其缺失会使免疫T细胞活化延迟或抑制至少50%。综上所述，这些结果表明ICAM-1对于快速T细胞活化、早期募集以及控制生殖道获得性沙眼衣原体至关重要。
