Institute of Medical Immunology, Charite-Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
Hum Immunol. 2012 Aug;73(8):844-51. doi: 10.1016/j.humimm.2012.04.008. Epub 2012 Apr 23.
HSV-1 persistently infects almost 90% of our population; however, only 30% of the infected subjects suffer from recurrent herpes lesions, most frequently herpes labialis (HL). We hypothesized that variations in toll-like receptor (TLR) functions might contribute to HL susceptibility. In our study, the TLR-2/1,-3, and -7/8 responses of immune cell subsets derived from asymptomatic HSV-1 carriers were compared with responses of subjects with HL history. Remarkably, natural killer (NK) cells isolated from HL subjects showed significantly lower IFN-γ responses selectively to the TLR3 agonist poly(I:C). Furthermore, the TLR3 L412F genetic polymorphism was found to reduce NK cell TLR3-responsiveness and is associated with susceptibility to recurrent HL. The TLR3 response detected in HL total peripheral blood mononuclear cells (PBMCs), however, was not impaired, indicating restoration of NK cell TLR3-deficiency through co-stimulatory functions. In conclusion, our results suggest that decreased TLR3 response of NK cells is associated with HL susceptibility; and potentially explain why symptomatic outbreak of HL usually occurs after stress or prolonged UV light exposure, when host co-stimulatory functions are disturbed.
单纯疱疹病毒 1 型几乎感染了我们 90%的人口；然而，只有 30%的感染者会出现复发性疱疹病变，最常见的是唇疱疹（HL）。我们假设 Toll 样受体（TLR）功能的变异可能导致 HL 易感性。在我们的研究中，我们比较了来自无症状 HSV-1 携带者的免疫细胞亚群与有 HL 病史的受试者的 TLR-2/1、-3 和 -7/8 反应。值得注意的是，从 HL 受试者中分离出的自然杀伤（NK）细胞对 TLR3 激动剂聚肌苷酸（poly（I：C））的 IFN-γ反应明显较低。此外，发现 TLR3 L412F 遗传多态性降低了 NK 细胞 TLR3 的反应性，并与复发性 HL 的易感性相关。然而，在 HL 总外周血单核细胞（PBMC）中检测到的 TLR3 反应并未受损，表明通过共刺激功能恢复了 NK 细胞 TLR3 缺陷。总之，我们的研究结果表明，NK 细胞 TLR3 反应降低与 HL 易感性相关；并可能解释为什么 HL 的症状性爆发通常发生在应激或长时间暴露于紫外线后，此时宿主共刺激功能受到干扰。
