<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>32</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">H Tima Giresse</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Innate signaling by mycolate esters of the cell wall of Mycobacterium tuberculosis and relevance for development of adjuvants for subunit vaccines</style></title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Adjuvants</style></keyword><keyword><style  face="normal" font="default" size="100%">Glucose monomycolate</style></keyword><keyword><style  face="normal" font="default" size="100%">Inflammasome</style></keyword><keyword><style  face="normal" font="default" size="100%">Innate immune responses</style></keyword><keyword><style  face="normal" font="default" size="100%">Mycolic Acids</style></keyword><keyword><style  face="normal" font="default" size="100%">Trehalose dimycolate</style></keyword><keyword><style  face="normal" font="default" size="100%">Tuberculosis</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2017</style></year><pub-dates><date><style  face="normal" font="default" size="100%">23/05/2017</style></date></pub-dates></dates><publisher><style face="normal" font="default" size="100%">Université de Liège</style></publisher><pub-location><style face="normal" font="default" size="100%">Liège, ​​Belgique</style></pub-location><pages><style face="normal" font="default" size="100%">229</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Tuberculosis remains among the most deadly health threats to humankind. This povertyrelated&amp;nbsp;disease, caused by bacteria of the Mycobacterium tuberculosis complex, kills each year&amp;nbsp;more than 1.5 million people. It is estimated that a further 2 billion individuals are latently&amp;nbsp;infected with M. tuberculosis. Most of them will never develop any clinical symptoms,&amp;nbsp;although 5 to 10% of these latently infected individuals are at risk to develop TB in their&amp;nbsp;lifetime. During the last decades the situation worsened because of deteriorating socioeconomic&amp;nbsp;conditions, the increased incidence of drug-resistant M.tuberculosis strains and the&amp;nbsp;co-infection with HIV (a major risk factor for development of TB). Currently only one vaccine&amp;nbsp;is available against TB, the Bacille of Calmette and Gu&amp;eacute;rin (BCG). However, its efficacy is&amp;nbsp;extremely variable against the contagious form of TB - pulmonary TB - in adults and&amp;nbsp;adolescents (ranging from 0 to 80%). Therefore, to control and eliminate TB, a better vaccine,&amp;nbsp;efficient drug treatments and more rapid and cheaper diagnostic techniques are needed.&amp;nbsp;&lt;/p&gt;

&lt;p&gt;In this PhD thesis we have attempted to provide additional information to reach this goal.&amp;nbsp;Indeed, we investigated the inflammatory and adjuvant potential of mycolate esters&amp;nbsp;&lt;br /&gt;
homologous of those found in the cell wall of M. tuberculosis. These mycolate esters vary in&amp;nbsp;terms of sugar (trehalose, glucose and arabinose) and lipid (alpha-, methoxy-, keto-, wax-ester&amp;nbsp;MAs) moieties. TDM, TMM, GMM and AraMM were found to be potent activators of BMDCs&amp;nbsp;in vitro. This activation was shown to be dependent on the Mincle pathway. Our results&amp;nbsp;demonstrated that the classes of MAs bound to sugar do not consistently impact the level of&amp;nbsp;pro-inflammatory and adjuvant responses induced. Rather, the nature of the sugar and the&amp;nbsp;number of acyl chains bound to it seem to dictate the affinity of the glycolipid for Mincle&amp;nbsp;receptor in vitro. In vivo, we observed that TDM, TMM and GMM induce similar immune&amp;nbsp;responses characterized by a production of antigen-specific IFN-&amp;gamma; and IL-17A. The immune&amp;nbsp;responses induced by AraMM are dependent on the type of formulation. Indeed, AraMM in&amp;nbsp;emulsion does not induce substantial level of Th1 while AraMM in DDA liposome induces Th1&amp;nbsp;immune response. This study increases our knowledge on host-pathogen interactions during&amp;nbsp;M. tuberculosis infection by identifying the receptor involved in the recognition of several&amp;nbsp;PAMPs. Furthermore, we showed that the activation of this receptor by these mycolate esters&amp;nbsp;triggers the induction of protective Th1 and Th17 immune responses.&lt;/p&gt;
</style></abstract><accession-num><style face="normal" font="default" size="100%">NA</style></accession-num></record></records></xml>