Innate immune lectins kill bacteria expressing blood group antigen.
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.
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.
Sean R
SR
Stowell
Connie M
CM
Arthur
Marcelo
M
Dias-Baruffi
Lilian C
LC
Rodrigues
Jean-Philippe
JP
Gourdine
Jamie
J
Heimburg-Molinaro
Tongzhong
T
Ju
Ross J
RJ
Molinaro
Carlos
C
Rivera-Marrero
Baoyun
B
Xia
David F
DF
Smith
Richard D
RD
Cummings
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001789:Blood Group Antigens / Q000276:immunology / Q000502:physiology*; D054308:Enteropathogenic Escherichia coli / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D000939:Epitopes; D004927:Escherichia coli Infections / Q000276:immunology*; D005434:Flow Cytometry; D037502:Galectin 3 / Q000276:immunology / Q000502:physiology; D037541:Galectin 4 / Q000276:immunology / Q000502:physiology*; D037161:Galectins / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology / Q000502:physiology*; D051379:Mice; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins
D000942:Antigens, Bacterial; D001789:Blood Group Antigens; D000939:Epitopes; D037502:Galectin 3; D037541:Galectin 4; D037161:Galectins; C091991:LGALS8 protein, human; D011994:Recombinant Proteins