Mycobacterium tuberculosis and the human macrophage – shifting the balance through inflammasome activation

.................................................................................................................. 1 POPULÄRVETENSKAPLIG SAMMANFATTNING ............................................. 3 LIST OF PAPERS ........................................................................................................ 5 ABBREVIATIONS ....................................................................................................... 6 BACKGROUND ........................................................................................................... 8 History of tuberculosis ................................................................................................ 8 Epidemiology .............................................................................................................. 9 The bacterium ............................................................................................................. 9 Evolution of Mycobacterium tuberculosis ............................................................ 10 The mycobacterial cell wall .................................................................................. 11 Mycobacterial secretion systems .......................................................................... 12 Pathogenesis .............................................................................................................. 12 Diagnosis and treatment ............................................................................................ 15 Diagnosis .............................................................................................................. 15 Treatment .............................................................................................................. 17 Vaccination ........................................................................................................... 17 Pathogen recognition in tuberculosis ........................................................................ 18 C-type lectins and complement receptor 3 ........................................................... 18 Toll-like receptors ................................................................................................. 20 Nucleotide-binding oligomerization domain-like receptors ................................. 21 Macrophage effector functions and Mycobacterium tuberculosis ............................ 24 Cytokine response ................................................................................................. 24 Macrophage activation and polarization ............................................................. 26 Phagosomal maturation ........................................................................................ 27 The fate of the mycobacterial phagosome ............................................................ 30 Autophagy ............................................................................................................. 33 Cell death .............................................................................................................. 35 Efferocytosis .......................................................................................................... 38 Antigen presentation ............................................................................................. 40