Lewis Blood-group Antigens Are Associated With Altered Susceptibility to Shigellosis

Abstract

In a cohort of infants, we found that lack of the Lewis histo-blood group antigen was associated with increased susceptibility to shigellosis. Broadly inhibiting fucosylation in epithelial cells in vitro decreased invasion by Shigella flexneri. These results support a role for fucosylated glycans in susceptibility to shigellosis.

Keywords: Lewis antigens; blood-group antigens; shigellosis.

Figure 1.

Lewis antigens are associated with altered susceptibility to shigellosis. A, Kaplan-Meier curve showing survival probability free from Shigella spp.–attributed diarrheal episode in the first year of life based on inferred Lewis and Secretor status (P < .01, log-rank test). The numbers of children who were at risk for Shigella spp.–attributed diarrhea are listed at the bottom of the table. B, HT-29 cells were treated with 2F-PAF or vehicle control for 3 days before infection. 2F-PAF treatment decreased the number of S. flexneri infection foci; the y axis shows infections per well normalized to input inoculum. n = 32 wells per treatment group. Data are combined from 4 independent experiments. C, 2F-PAF treatment did not alter S. flexneri infection foci area (spread). n = 28 wells per treatment group. Data are combined from 3 independent experiments Significance for both B and C was determined by a 2-tailed nonparametric Mann–Whitney U test, *P < .05. Abbreviations: A.U., arbitrary units; L+, Lewis positive; L−, Lewis negative; ns, not significant; S+, Secretor positive; S–, Secretor negative; 2F-PAF, 2F-peracetyl-fucose.