%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Lembo-Fazio, L.
%A Billod, J. M.
%A Di Lorenzo, F.
%A Paciello, I.
%A Pallach, M.
%A Vaz-Francisco, S.
%A Holgado, A.
%A Beyaert, R.
%A Fresno, M.
%A Shimoyama, A.
%A Lanzetta, R.
%A Fukase, K.
%A Gully, Djamel
%A Giraud, Eric
%A Martin-Santamaria, S.
%A Bernardini, M. L.
%A Silipo, A.
%T Bradyrhizobium Lipid A : immunological properties and molecular basis of its binding to the myeloid differentiation protein-2/toll-like receptor 4 complex
%D 2018
%L fdi:010073729
%G ENG
%J Frontiers in Immunology
%@ 1664-3224
%K lipopolysaccharide ; innate immunity ; inflammatory cytokines ; myeloid ; differentiation protein-2/toll-like receptor 4 ; Bradyrhizobium lipid A ; molecular modeling
%M ISI:000441656100001
%P art. 1888 [14 ]
%R 10.3389/fimmu.2018.01888
%U https://www.documentation.ird.fr/hor/fdi:010073729
%> https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers18-09/010073729.pdf
%V 9
%W Horizon (IRD)
%X Lipopolysaccharides (LPS) are potent activator of the innate immune response through the binding to the myeloid differentiation protein-2 (MD-2)/toll-like receptor 4 (TLR4) receptor complexes. Although a variety of LPSs have been characterized so far, a detailed molecular description of the structure-activity relationship of the lipid A part has yet to be clarified. Photosynthetic Bradyrhizobium strains, symbiont of Aeschynomene legumes, express distinctive LPSs bearing very long-chain fatty acids with a hopanoid moiety covalently linked to the lipid A region. Here, we investigated the immunological properties of LPSs isolated from Bradyrhizobium strains on both murine and human immune systems. We found that they exhibit a weak agonistic activity and, more interestingly, a potent inhibitory effect on MD-2/TLR4 activation exerted by toxic enterobacterial LPSs. By applying computational modeling techniques, we also furnished a plausible explanation for the Bradyrhizobium LPS inhibitory activity at atomic level, revealing that its uncommon lipid A chemical features could impair the proper formation of the receptorial complex, and/or has a destabilizing effect on the pre-assembled complex itself.
%$ 020 ; 084 ; 050