Regulation of innate immune responses by the TPL-2/ABIN-2/NF-κB1 p105 complex

The innate immune response is the immediate protective reaction of the body to infection and essential to kill invading bacterial pathogens. A key component of this response is the ingestion of bacteria by macrophages (a type of innate immune cell) using a process called phagocytosis. The internalised bacteria are trapped in membrane-bound sacs called phagosomes, which then mature to alter their composition and trigger bacterial killing. We have recently discovered that the TPL-2 complex, comprised of three proteins working together in a group inside macrophages, stimulates phagosome maturation. We aim to determine the mechanism by which the TPL-2 complex induces phagosome maturation and how this controls immune responses to pathogenic bacteria and inflammatory bowel disease (IBD) pathogenesis, which depends on bacteria in the gut. These studies will increase our understanding of a fundamental aspect of the innate immune response and may identify novel therapeutic targets for bacterial diseases and IBD.