Induction and functional role of type I interferon in bacterial infection of macrophages

Infection represents an evolutionary arms race between pathogen and host. Thus, scientists find that pathogenic microbes have evolved elegant strategies to manipulate or avoid our immune system, allowing them to persist within the human population. This thesis is largely focused on how bacteria regulate and exploit the type I interferon (IFN) response in infected macrophages – a processes of central importance to cellular immunity and bacterial pathogenesis. More specifically, we have been interested in understanding how Streptococcus pyogenes and mycobacteria – representing evolutionarily distant pathogens causing acute and chronic infections, respectively – interact with macrophages to induce and functionally exploit the type I IFN response. Our studies have identified a specific streptococcal component, the surface M protein, and the mechanisms underlying induction of the type I IFN response in infected macrophages. In the case of mycobacterial infection, we provide new insight into the genetic requirements and mechanisms for ESX-1-mediated type I IFN induction, and describe a macrophage-modulating role for induced type I IFN that can be exploited by the bacteria to avoid being cleared by the immune system.