Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.
Nat Med. 2010 Mar;16(3):295-301. doi: 10.1038/nm.2103. Epub 2010 Feb 14.
The expression of ABO(H) blood group antigens causes deletion of cells that generate self-specific antibodies to these antigens but this deletion limits adaptive immunity toward pathogens bearing cognate blood group antigens. To explore potential defense mechanisms against such pathogens, given these limitations in adaptive immunity, we screened for innate proteins that could recognize human blood group antigens. Here we report that two innate immune lectins, galectin-4 (Gal-4) and Gal-8, which are expressed in the intestinal tract, recognize and kill human blood group antigen-expressing Escherichia coli while failing to alter the viability of other E. coli strains or other Gram-negative or Gram-positive organisms both in vitro and in vivo. The killing activity of both Gal-4 and Gal-8 is mediated by 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 express blood group-like antigens on their surface.
ABO(H) 血型抗原的表达导致产生针对这些抗原的自身特异性抗体的细胞缺失，但这种缺失限制了针对具有同源血型抗原的病原体的适应性免疫。为了探索针对此类病原体的潜在防御机制，鉴于适应性免疫的这些限制，我们筛选了能够识别人类血型抗原的先天蛋白。在这里，我们报告说，两种先天免疫凝集素，半乳糖凝集素-4（Gal-4）和 Gal-8，在肠道中表达，能够识别和杀死表达人类血型抗原的大肠杆菌，而不会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体的活力，无论是在体外还是体内。Gal-4 和 Gal-8 的杀伤活性均由其 C 末端结构域介导，快速发生，独立于补体，并伴有膜完整性的破坏。这些结果表明，先天防御凝集素可以提供针对表面表达血型样抗原的病原体的免疫。
