A transcriptomic approach for studying the activation of dendritic cells in response to mycobacterial infections

...............................................................................................................3 Acknowledgements ..............................................................................................4 List of abbreviations...........................................................................................16 List of Figures...................................................................................12 List of Tables................................................................................15 Chapter 1-Introduction 1.1Tuberculosisa global disease .....................................................................20 1.2M. tuberculosis............................................................................................22 1.2.1M. tuberculosis aetiological agent of TB.........................................22 1.2.2Pathogenesis of tuberculosis .............................................................23 1.2.3Interplay between host and pathogen ................................................24 1.2.4Interaction between macrophages and M. tuberculosis ......................24 1.2.5Antimycobacterial mechanisms of the macrophage...........................25 1.2.6Immune evasion mechanisms employed by M. tuberculosis..............26 1.3Dendritic cellssentinels of the immune system ..........................................29 1.3.1Dendritic cell subsets ........................................................................30 1.3.2Immature dendritic cells ...................................................................32 1.3.3Dendritic cell maturation and migration ............................................32 1.3.4Phagocytic receptors on dendritic cells .............................................33 1.4Activation of cellular signalling pathways ...................................................35 1.4.1Adaptors involved in TLR signalling pathways.................................35 1.4.2MyD88 dependent and independent TLR signalling pathways ..........36 1.4.3Negative regulators of the TLR signalling pathway...........................39 1.4.4Interaction between TLRs and microbes ...........................................40 1.4.5Role of TLRs in the immune response to mycobacteria.....................41 1.5Type I IFNs.................................................................................................43