Bezbradica Mirkovic Group | Innate Immunity and Inflammation
The overall goal of our research is to understand inflammatory responses to sterile versus microbe-induced tissue injury.
The purpose of the inflammatory response is context-dependent. During infection, inflammation aims to eliminate the insult and induce protective immunity, while inflammation triggered by sterile injury aims to limit the damage and enable tissue repair. In most cases, the same immune cells, receptors and signalling pathways control both types of responses, and it is currently poorly understood how such a system directs a response that is tailored to its inducer. Addressing this major knowledge gap will allow us to design therapies against inflammatory diseases caused by sterile injury without compromising the patient’s antimicrobial defences.
The main objectives of the lab are to understand:
1. How is inflammatory response initiated?
We will continue to investigate how tissue resident immune cells such as macrophages integrate signals from cytokines (soluble mediators that report on tissue injury) with signals from microbial and tissue-damage sensors to direct a response that is tailored to a specific pathophysiologic situation. Specifically, we will study a novel class of cytokine-regulated signalling adapters and their role in shaping immune responses to sterile and microbial tissue injury.
2. How is inflammatory response tailored to its inducer (e.g. in sterile versus microbe-induced injury)?
We will use a combination of genomic and proteomic approaches to investigate and compare responses elicited by infectious agents, necrotic/apoptotic cells or necrotic/apoptotic cells carrying an infectious agent. Tissue resident innate cells such as macrophages, and their innate sensors such as NLRP3 inflammasome, are sentinels of tissue homeostasis and will thus serve as a cellular model for these investigations.