Department of Virology, Swedish Institute for Infectious Disease Control, 17157, Solna, Sweden.
HD Department of Clinical Virology, Stockholm, Sweden.
Sci Rep. 2018 Jul 5;8(1):10180. doi: 10.1038/s41598-018-28242-y.
The importance of natural IgM antibodies in protection against infections is still emerging and these antibodies have a potential role in the maintenance of homeostasis through clearance of apoptotic bodies, complement-dependent mechanisms, inflammation and exclusion of misfolded proteins. Natural IgM act as a first line of defence against unknown hazardous factors and are present in most vertebrates. We investigated the functional capacity of anti-HIV-1 IgM monoclonal antibodies, from a combinatorial Fab library derived from healthy individuals, and evaluated their protective role in inhibiting HIV-1 in vitro when passing across the human mucosal epithelial barrier. Primary HIV-1 isolates were efficiently transmitted over the tight polarized epithelial cells when added to their apical surface. Efficient inhibition of HIV-1 transmission was achieved when anti-HIV-1 IgM monoclonal antibodies were added to the basolateral side of the cells. Two of these human IgM MoAbs had the ability to neutralize HIV and reduced infection of dendritic cells in primary cervico-vaginal tissue biopsies in vitro. This indicates a potential role of natural IgM antibodies in the reduction of HIV-1 transmission in mucosal tissues and improve our understanding of how natural IgM antibodies against a neutralizing epitope could interfere with viral transmission.
天然 IgM 抗体在抗感染中的重要性尚在不断显现，这些抗体通过清除凋亡小体、补体依赖性机制、炎症和排除错误折叠的蛋白质，在维持体内平衡方面具有潜在作用。天然 IgM 作为抵御未知有害因素的第一道防线存在于大多数脊椎动物中。我们研究了来自健康个体的组合 Fab 文库中抗 HIV-1 IgM 单克隆抗体的功能能力，并评估了当它们穿过人黏膜上皮屏障时，在体外抑制 HIV-1 的保护作用。当将原发性 HIV-1 分离物添加到其顶端表面时，它们可以有效地穿过紧密极化的上皮细胞进行传播。当将抗 HIV-1 IgM 单克隆抗体添加到细胞的基底外侧时，可以有效地抑制 HIV-1 的传播。其中两种人 IgM MoAbs 具有中和 HIV 的能力，并减少了体外原代宫颈阴道组织活检中树突状细胞的感染。这表明天然 IgM 抗体在减少黏膜组织中 HIV-1 传播方面具有潜在作用，并增进了我们对针对中和表位的天然 IgM 抗体如何干扰病毒传播的理解。
