Inflammatory Properties and Adjuvant Potential of Synthetic Glycolipids Homologous to Mycolate Esters of the Cell Wall of Mycobacterium tuberculosis

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Tima HG, Al Dulayymi JR, Denis O, Lehebel P, Baols KS, Mohammed MO, L'Homme L, Sahb MM, Potemberg G, Legrand S, Lang R, Beyaert R, Piette J, Baird MS, Huygen K, Romano M
Zeitschrift: Journal of Innate Immunity
Jahr der Veröffentlichung: 2017
Band: 9
Heftnummer: 2
Seitenbereich: 162-180
ISSN: 1662-811X


Abstract


The cell wall of mycobacteria is characterised by glycolipids composed of different classes of mycolic acids (MAs; alpha-, keto-, and methoxy-) and sugars (trehalose, glucose, and arabinose). Studies using mutant Mtb strains have shown that the structure of MAs influences the inflammatory potential of these glycolipids. As mutant Mtb strains possess a complex mixture of glycolipids, we analysed the inflammatory potential of single classes of mycolate esters of the Mtb cell wall using 38 different synthetic analogues. Our results show that synthetic trehalose dimycolate (TDM) and trehalose, glucose, and arabinose monomycolates (TMM, GMM, and AraMM) activate bone marrow-derived dendritic cells in terms of the production of pro-inflammatory cytokines (IL-6 and TNF-?) and reactive oxygen species, upregulation of costimulatory molecules, and activation of NLRP3 inflammasome by a mechanism dependent on Mincle. These findings demonstrate that Mincle receptor can also recognise pentose esters and seem to contradict the hypothesis that production of GMM is an escape mechanism used by pathogenic mycobacteria to avoid recognition by the innate immune system. Finally, our experiments indicate that TMM and GMM, as well as TDM, can promote Th1 and Th17 responses in mice in an OVA immunisation model, and that further analysis of their potential as novel adjuvants for subunit vaccines is warranted.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Lang, Roland Prof. Dr.
Professur für Angeborene Immunität und Pathogenerkennung


Einrichtungen weiterer Autorinnen und Autoren

Bangor University
Belgian Scientific Institute of Public Health / Wetenschappelijk Instituut Volksgezondheid / Institut Scientifique de Santé Publique (WIV-ISP)
Universiteit Gent (UGent) / Ghent University
University of Liège (ULg) / Université de Liège


Zitierweisen

APA:
Tima, H.G., Al Dulayymi, J.R., Denis, O., Lehebel, P., Baols, K.S., Mohammed, M.O.,... Romano, M. (2017). Inflammatory Properties and Adjuvant Potential of Synthetic Glycolipids Homologous to Mycolate Esters of the Cell Wall of Mycobacterium tuberculosis. Journal of Innate Immunity, 9(2), 162-180. https://dx.doi.org/10.1159/000450955

MLA:
Tima, Hermann Giresse, et al. "Inflammatory Properties and Adjuvant Potential of Synthetic Glycolipids Homologous to Mycolate Esters of the Cell Wall of Mycobacterium tuberculosis." Journal of Innate Immunity 9.2 (2017): 162-180.

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Zuletzt aktualisiert 2018-10-10 um 08:21