Mucosal Immunology Unit at Guy's Hospital, King's College London, London, UK.
Curr Opin HIV AIDS. 2011 Sep;6(5):398-404. doi: 10.1097/COH.0b013e3283499df7.
To present evidence of the role of innate mucosal immunity and to harness this arm of immunity in protection against HIV infection.
Dendritic cells, monocytes, natural killer (NK) cells and γδ T cells are critical in innate immunity, which is mediated by Toll-like receptor (TLR) and recently identified stress pathways. Complement factors, cytokines and chemokines have diverse functions usually affecting HIV infection indirectly. A novel group of innate intracellular HIV restriction factors has been identified - APOBEC3G, TRIM5α and tetherin - all of which are upregulated by type I interferons and some by vaccination and TLR agonists. Whereas innate immunity conventionally lacks memory, recent evidence suggests that some of the cells and intracellular factors may express immunological memory-like features.
Innate mucosal immunity may provide early effective control of HIV transmission and replication. Some vaccines can enhance innate immune factors, such as APOBEC3G and control HIV during the eclipse period, allowing full weight of neutralizing and/or cytotoxic T cells to develop and prevent mucosal HIV infection. The next generation of vaccines should be designed to target both innate and adaptive immune memory responses.
介绍固有黏膜免疫的作用,并利用这一免疫机制来预防 HIV 感染。
树突状细胞、单核细胞、自然杀伤 (NK) 细胞和 γδ T 细胞在固有免疫中起关键作用,固有免疫由 Toll 样受体 (TLR) 和最近确定的应激途径介导。补体因子、细胞因子和趋化因子具有多种功能,通常间接影响 HIV 感染。一组新的固有细胞内 HIV 限制因子已被确定 - APOBEC3G、TRIM5α 和 tetherin - 所有这些因子均由 I 型干扰素和一些疫苗及 TLR 激动剂上调。虽然固有免疫通常缺乏记忆,但最近的证据表明,一些细胞和细胞内因子可能具有免疫记忆样特征。
固有黏膜免疫可能提供对 HIV 传播和复制的早期有效控制。一些疫苗可以增强固有免疫因子,如 APOBEC3G,并在潜伏期控制 HIV,从而使中和和/或细胞毒性 T 细胞充分发挥作用,防止黏膜 HIV 感染。下一代疫苗的设计应针对固有和适应性免疫记忆反应。