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.
Stowell
Sean R
SR
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, USA.
Arthur
Connie M
CM
Dias-Baruffi
Marcelo
M
Rodrigues
Lilian C
LC
Gourdine
Jean-Philippe
JP
Heimburg-Molinaro
Jamie
J
Ju
Tongzhong
T
Molinaro
Ross J
RJ
Rivera-Marrero
Carlos
C
Xia
Baoyun
B
Smith
David F
DF
Cummings
Richard D
RD
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