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Innate immune lectins kill bacteria expressing blood group antigen

2010; Nature Portfolio; Volume: 16; Issue: 3 Linguagem: Inglês

10.1038/nm.2103

1546-170X

Sean R. Stowell, Connie M. Arthur, Marcelo Dias‐Baruffi, Lílian Cataldi Rodrigues, Jean-Philippe F. Gourdine, Jamie Heimburg‐Molinaro, Tongzhong Ju, Ross J. Molinaro, Carlos A. Rivera-Marrero, Baoyun Xia, David F. Smith, Richard D. Cummings,

Complement system in diseases

The expression of blood group antigens causes deletion of cells that generate self-specific antibodies to those antigens, but this deletion could limit adaptive immunity toward pathogens bearing cognate antigens. Two innate immune lectins, galectin-4 and galectin-8, are now reported to recognize and kill human blood group antigen–expressing bacteria. 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 ( pages 263 –264 ).