Hirbod Taha, Reichard Camilla, Hasselrot Klara, Söderlund Johan, Kimani Joshua, Bwayo Job J, Plummer Francis, Kaul Rupert, Broliden Kristina
Infectious Diseases Unit, Department of Medicine, Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Sweden.
Curr HIV Res. 2008 Jan;6(1):28-33. doi: 10.2174/157016208783571964.
Mucosal HIV-1 exposure stimulates a variety of mucosal immune responses, including IgA1-mediated virus neutralization, even in the absence of an established infection. We hypothesized that other immune molecules might also contribute to the HIV-1 neutralizing activity observed in the mucosal secretions of HIV-1 exposed uninfected individuals.
Saliva samples were collected from HIV-1 seronegative high-risk female sex workers (FSW) from Nairobi. Samples were also collected from HIV-1 IgG positive FSW and HIV-1 IgG negative low-risk women from the same geographical area. In all samples, IgA2, secretory leukocyte protease inhibitor (SLPI), regulated on activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein 1 alpha and beta (MIP-1alpha and -beta) and monocyte chemoattractant protein-1 (MCP-1) were quantified. The IgA1-depleted saliva samples were subsequently tested for neutralizing capacity in a PBMC-based neutralization assay using a primary HIV-1 clade A isolate to determine biological relevance of the measured molecules.
HIV-1 specific neutralization was present in the IgA1-depleted fraction from saliva of both HIV-1 seropositive (9 of 10) and high-risk individuals (36 of 45) but not in HIV-1 IgG-negative control subjects (0 of 8). In the high-risk individuals, higher levels of CC-chemokines were seen in those that could neutralize HIV-1 as compared with those that could not (P<0.05).
The HIV-1 neutralizing activity in saliva of HIV-1-exposed high-risk individuals is not only mediated by IgA1, but is also present in IgA1-depleted fractions and is associated with increased levels of CC-chemokines. Such innate immune factors may be important in limiting HIV-1 mucosal transmission.
即使在未发生明确感染的情况下，黏膜暴露于HIV-1也会刺激多种黏膜免疫反应，包括IgA1介导的病毒中和作用。我们推测，其他免疫分子可能也有助于在暴露于HIV-1但未感染个体的黏膜分泌物中观察到的HIV-1中和活性。
从内罗毕的HIV-1血清阴性高危女性性工作者（FSW）中收集唾液样本。还从同一地理区域的HIV-1 IgG阳性FSW和HIV-1 IgG阴性低危女性中收集样本。对所有样本中的IgA2、分泌型白细胞蛋白酶抑制剂（SLPI）、活化调节正常T细胞表达和分泌因子（RANTES）、巨噬细胞炎性蛋白1α和β（MIP-1α和-β）以及单核细胞趋化蛋白-1（MCP-1）进行定量。随后，使用一株HIV-1 A亚型原始分离株，在基于外周血单个核细胞（PBMC）的中和试验中检测去除IgA1后的唾液样本的中和能力，以确定所测分子的生物学相关性。
HIV-1特异性中和作用存在于HIV-1血清阳性个体（10例中的9例）和高危个体（45例中的36例）唾液中去除IgA1的部分，但在HIV-1 IgG阴性对照个体（8例中的0例）中不存在。在高危个体中，与不能中和HIV-1的个体相比，能中和HIV-1的个体中CC趋化因子水平更高（P<0.05）。
暴露于HIV-1的高危个体唾液中的HIV-1中和活性不仅由IgA1介导，在去除IgA1的部分中也存在，并且与CC趋化因子水平升高有关。此类天然免疫因子可能在限制HIV-1黏膜传播方面具有重要作用。
