Laboratory of Molecular Microbiology, Program in Barrier Immunity and Repair, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2013 Mar 15;190(6):2959-65. doi: 10.4049/jimmunol.1202319. Epub 2013 Feb 11.
During HIV/SIV infection, mucosal immune system dysfunction and systemic immune activation are associated with progression to AIDS; however, it is unclear to what extent pre-existing gastrointestinal damage relates to disease progression postinfection. Pigtail macaques (PTM) are an excellent model in which to assess mucosal dysfunction in relation to HIV/SIV pathogenesis, as the majority of these animals have high levels of gastrointestinal damage, immune activation, and microbial translocation prior to infection, and rapidly progress to AIDS upon SIV infection. In this study, we characterized the mucosal immune environment prior to and throughout SIV infection in 13 uninfected PTM and 9 SIV-infected PTM, of which 3 were slow progressors. This small subset of slow progressors had limited innate immune activation in mucosal tissues in the periphery, which was associated with a more intact colonic epithelial barrier. Furthermore, we found that preinfection levels of microbial translocation, as measured by LPS-binding protein, in PTM correlated with the rate of progression to AIDS. These data suggest that pre-existing levels of microbial translocation and gastrointestinal tract dysfunction may influence the rate of HIV disease progression.
在 HIV/SIV 感染期间，黏膜免疫系统功能障碍和全身免疫激活与艾滋病的进展相关；然而，目前尚不清楚感染前胃肠道损伤在多大程度上与感染后的疾病进展相关。长尾猕猴（PTM）是评估与 HIV/SIV 发病机制相关的黏膜功能障碍的极佳模型，因为这些动物在感染前大多数都有高水平的胃肠道损伤、免疫激活和微生物易位，并且在感染 SIV 后迅速进展为艾滋病。在这项研究中，我们在 13 只未感染的 PTM 和 9 只感染 SIV 的 PTM 中，对 SIV 感染前和感染期间的黏膜免疫环境进行了特征描述，其中 3 只为缓慢进展者。这一小部分缓慢进展者在外周黏膜组织中固有免疫激活有限，这与更完整的结肠上皮屏障有关。此外，我们发现，PTM 中脂多糖结合蛋白测量的微生物易位的感染前水平与艾滋病进展的速度相关。这些数据表明，先前存在的微生物易位和胃肠道功能障碍水平可能会影响 HIV 疾病进展的速度。
