Mycobacterial regulation of macrophage responses to infection: Induction and functional role of type I interferon

Infection represents a complex interplay between invading microorganisms and the immune system. The immune system dynamically responds to the presence of pathogens, employing various defence mechanisms to neutralize and eliminate invaders. However, pathogens have evolved strategies to evade detection and elimination, leading to infections. This thesis focuses on mycobacterial regulation of macrophages, a key interplay in the pathogenesis of tuberculosis. The macrophage aims to neutralize intruding mycobacteria through the process of phagocytosis, however, Mycobacterium tuberculosis evades the phagosome, allowing it to gain access to the cytosol of the macrophage. From here it manipulates macrophage functions and other immune responses. The specialized protein secretion system ESX-1 is required for full virulence of mycobacteria and is involved in evasion strategies such as phagosomal escape and induction of type I interferons. The role of type I interferons in mycobacterial infection remains incompletely understood, although evidence strongly suggests a host detrimental role. The work presented in this thesis brings light on these key events during mycobacterial infection and contributes with new insights regarding the onset and functional role of the type I interferon response during infection.