Hibma Merilyn H
Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin, New Zealand.
Open Virol J. 2012;6:241-8. doi: 10.2174/1874357901206010241. Epub 2012 Dec 28.
Human papillomavirus (HPV) infections cause a significant global health burden, predominantly due to HPV-associated cancers. HPV infects only the epidermal cells of cutaneous and mucosal skin, without penetration into the dermal tissues. Infections may persist for months or years, contributed by an array of viral immune evasion mechanisms. However in the majority of cases immunity-based regression of HPV lesions does eventually occur. The role of the innate immune response to HPV in persistence and regression of HPV infection is not well understood. Although an initial inflammatory infiltrate may contribute to disease regression, sustained inflammation at the HPV-induced lesions, characterized by macrophage and neutrophil infiltration, has been observed in persistence. Pathogen-associated molecular patterns (PAMPs) are important in innate recognition. The double stranded DNA and an L1 and L2 capsid components of the HPV virion are potential PAMPs that can trigger signaling through cellular pattern recognition receptors, including toll-like receptors (TLR). TLR expression is increased in regressing HPV disease but is reduced in persistent lesions, suggesting a role for TLR in HPV regression. With regard to the adaptive immune response, a key indicator of regression in humans is infiltration of the lesion with both CD4 and CD8 T cells. In individuals with persistent lesions, CD8 T cell and immune suppressive regulatory T cells (Tregs) infiltrate the infection site. There is no association between persistence or regression and the presence of serum antibodies to the viral capsid antigens of HPV. There is still much to be learned about the immunological events that trigger regression of HPV disease. Understanding the viral and host factors that influence persistence and regression is important for the development of better immunotherapeutic treatments for HPV-associated disease.
人乳头瘤病毒（HPV）感染给全球带来了沉重的健康负担，这主要归因于HPV相关癌症。HPV仅感染皮肤和黏膜皮肤的表皮细胞，不会侵入真皮组织。由于一系列病毒免疫逃逸机制，感染可能持续数月或数年。然而，在大多数情况下，基于免疫的HPV病变消退最终还是会发生。先天免疫反应在HPV持续感染和消退过程中的作用尚未完全明确。虽然最初的炎症浸润可能有助于疾病消退，但在持续感染中，已观察到HPV诱导病变处持续存在以巨噬细胞和中性粒细胞浸润为特征的炎症。病原体相关分子模式（PAMPs）在先天识别中很重要。HPV病毒颗粒的双链DNA以及L1和L2衣壳成分是潜在的PAMPs，可通过细胞模式识别受体（包括Toll样受体（TLR））触发信号传导。在消退的HPV疾病中TLR表达增加，但在持续病变中则降低，这表明TLR在HPV消退中发挥作用。关于适应性免疫反应，人类疾病消退的一个关键指标是病变处有CD4和CD8 T细胞浸润。在持续病变的个体中，CD8 T细胞和免疫抑制性调节性T细胞（Tregs）浸润感染部位。HPV病毒衣壳抗原的血清抗体的存在与持续感染或消退之间没有关联。关于触发HPV疾病消退的免疫事件，仍有许多有待了解的地方。了解影响持续感染和消退的病毒和宿主因素对于开发更好的针对HPV相关疾病的免疫治疗方法很重要。
