Helicobacter pylori is a
prevalent bacterial,
gastroduodenal pathogen of humans that can express Lewis (Le) and related
antigens in the O-chains of its surface
lipopolysaccharide. The O-chains of
H. pylori are commonly composed of internal Le(x) units with terminal Le(x) or Le(y) units or, in some strains, with additional units of Le(a), Le(b), Le(c), sialyl-Le(x) and H-1
antigens, as well as
blood groups A and B, thereby producing a
mosaicism of
antigenic units expressed. The
genetic determination of the Le
antigen biosynthetic pathways in
H. pylori has been studied, and despite striking functional similarity, low
sequence homology occurs between the
bacterial and mammalian alpha(1,3/4)- and alpha(1,2)-
fucosyltransferases. Factors affecting Le
antigen expression in
H. pylori, that can influence the biological impact of this
molecular mimicry, include regulation of
fucosyltransferase genes through
slipped-strand mispairing, the activity and expression levels of the functional
enzymes, the preferences of the expressed
enzyme for distinctive acceptor molecules and the availability of activated
sugar intermediates. Le mimicry was initially implicated in
immune evasion and
gastric adaptation by the
bacterium, but more recent studies show a role in
gastric colonization and
bacterial adhesion with galectin-3 identified as the
gastric receptor for
polymeric Le(x) on the
bacterium. From the host defence aspect, innate
immune recognition of
H. pylori by
surfactant protein D is influenced by the extent of LPS fucosylation. Furthermore, Le
antigen expression affects both the
inflammatory response and
T-cell polarization that develops after
infection. Although controversial, evidence suggests that long-term
H. pylori infection can induce autoreactive anti-Le
antibodies cross-reacting with the
gastric mucosa, in part leading to the development of
gastric atrophy. Thus, Le
antigen expression and fucosylation in
H. pylori have multiple biological effects on
pathogenesis and disease outcome.
