Innate immune lectins kill bacteria expressing blood group antigen.
Innate immune lectins kill bacteria expressing blood group antigen.
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ABO(H) 血型抗原的表达导致产生自身抗血型抗体的细胞缺失，但这种缺失限制了对具有同源血型抗原的病原体的适应性免疫。为了探索针对这些病原体的潜在防御机制，考虑到适应性免疫的局限性，我们筛选了可以识别人类血型抗原的先天蛋白。在这里，我们报道了两种在肠道中表达的先天免疫凝集素，半乳糖凝集素-4和-8，识别并杀死表达人类血型抗原的大肠杆菌，但在体外和体内均不能改变其他大肠杆菌菌株或其他革兰氏阴性或革兰氏阳性生物的活力。半乳糖凝集素-4 和-8 的杀伤作用均位于其 C 末端结构域内，发生迅速且独立于补体，并且伴随着膜完整性的破坏。这些结果表明，先天防御凝集素可以提供针对表面具有血型自身抗原的病原体的免疫力。
The expression of ABO(H) blood group antigens causes deletion of cells that generate self anti-blood group antibodies, but this deletion limits adaptive immunity toward pathogens bearing cognate blood group antigens. To explore potential defense mechanisms against these pathogens, given such limitations in adaptive immunity, we screened for innate proteins that could recognize human blood group antigens. Here we report that two innate immune lectins, galectins-4 and -8, which are expressed in the intestinal tract, recognize and kill human blood group antigen-expressing E. coli, while failing to alter viability of other E. coli strains or other gram-negative or gram-positive organisms both in vitro and in vivo. Killing by both galectins-4 and -8 resides within their C-terminal domains, occurs rapidly and independently of complement, and is accompanied by disruption of membrane integrity. These results demonstrate that innate defense lectins can provide immunity against pathogens that display blood group self-antigens on their surface.