The gut microbiota guide the development
of the host immune system
by setting a systemic threshold for immune activation. Lipopolysaccharides
(LPSs) from gut bacteria are able to trigger systemic and local proinflammatory
and immunomodulatory responses, and this capability strongly relies
on their fine structures. Up to now, only a few LPS structures from
gut commensals have been elucidated; therefore, the molecular motifs
that may be important for LPS–mammalian cell interactions at
the gut level are still obscure. Here, we report on the full structure
of the LPS isolated from one of the prominent species of the genus
Bacteroides
,
Bacteroides vulgatus
. The
LPS turned out to consist of a particular chemical structure based
on hypoacylated and
mono
-phosphorylated lipid A and
with a galactofuranose-containing core oligosaccharide and an O-antigen
built up of mannose and rhamnose. The evaluation of the immunological
properties of this LPS on human
in vitro
models revealed
a very interesting capability to produce anti-inflammatory cytokines
and to induce a synergistic action of MD-2/TLR4- and TLR2-mediated
signaling pathways.
Alcaligenes faecalis is the predominant Gramnegative bacterium inhabiting gut-associated lymphoid tissues, Peyersp atches.W ep reviously reported that an A. faecalis lipopolysaccharide (LPS) acted as aweak agonist for Toll-like receptor 4( TLR4)/myeloid differentiation factor-2 (MD-2) receptor as well as ap otent inducer of IgA without excessive inflammation, thus suggesting that A. faecalis LPS might be used as as afe adjuvant. In this study,w ec haracterized the structure of both the lipooligosaccharide (LOS) and LPS from A. faecalis.W esynthesized three lipid Amolecules with different degrees of acylation by an efficient route involving the simultaneous introduction of 1-and 4'-phosphates.H exaacylated A. faecalis lipid As howed moderate agonistic activity towards TLR4-mediated signaling and the ability to elicit adiscrete interleukin-6 release in human cell lines and mice.It was thus found to be the active principle of the LOS/LPS and apromising vaccine adjuvant candidate.
Alcaligenes faecalis is the predominant Gramnegative bacterium inhabiting gut-associated lymphoid tissues, Peyersp atches.W ep reviously reported that an A. faecalis lipopolysaccharide (LPS) acted as aweak agonist for Toll-like receptor 4( TLR4)/myeloid differentiation factor-2 (MD-2) receptor as well as ap otent inducer of IgA without excessive inflammation, thus suggesting that A. faecalis LPS might be used as as afe adjuvant. In this study,w ec haracterized the structure of both the lipooligosaccharide (LOS) and LPS from A. faecalis.W esynthesized three lipid Amolecules with different degrees of acylation by an efficient route involving the simultaneous introduction of 1-and 4'-phosphates.H exaacylated A. faecalis lipid As howed moderate agonistic activity towards TLR4-mediated signaling and the ability to elicit adiscrete interleukin-6 release in human cell lines and mice.It was thus found to be the active principle of the LOS/LPS and apromising vaccine adjuvant candidate.
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