AUTHOR=Lembo-Fazio Luigi , Billod Jean-Marc , Di Lorenzo Flaviana , Paciello Ida , Pallach Mateusz , Vaz-Francisco Sara , Holgado Aurora , Beyaert Rudi , Fresno Manuel , Shimoyama Atsushi , Lanzetta Rosa , Fukase Koichi , Gully Djamel , Giraud Eric , Martín-Santamaría Sonsoles , Bernardini Maria-Lina , Silipo Alba TITLE=Bradyrhizobium Lipid A: Immunological Properties and Molecular Basis of Its Binding to the Myeloid Differentiation Protein-2/Toll-Like Receptor 4 Complex JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01888 DOI=10.3389/fimmu.2018.01888 ISSN=1664-3224 ABSTRACT=

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.