Bezbradica Mirkovic Group | Innate Immune Sensing in Inflammation

Introduction: 

Inflammation is essential for host defence and tissue repair, but when uncontrolled it becomes a major driver of chronic disease, including arthritis, neurodegeneration, cardiovascular disease, and cancer.

Our research investigates how macrophages use inflammasomes, inflammatory cell death, and intercellular communication to sense tissue damage and shape sterile inflammation.

Macrophages are central to this process because they integrate signals from tissue damage, inflammatory mediators, and the local microenvironment to determine the magnitude, quality, and duration of inflammatory responses. Using molecular, cellular, and in vivo approaches, we investigate the mechanisms that enable macrophages to sense tissue perturbation and coordinate inflammatory responses within tissues.

Major research objectives

1. Inflammasomes and inflammatory cell death in sterile inflammation.

Inflammasomes are key innate immune sensors, highly expressed in macrophages, that detect cellular stress and tissue damage. Their activation promotes the release of inflammatory cytokines and triggers inflammatory cell death pathways that profoundly influence tissue inflammation.

A major focus of our laboratory is understanding how inflammasome activity and inflammatory cell death are regulated within tissues, and how these pathways interact with the tissue inflammatory environment. We are particularly interested in the NLRP3 inflammasome, a central driver of chronic inflammatory and age-associated diseases.

In parallel, we investigate the immunological consequences of lytic cell death and how signals released from dying cells shape inflammation, tissue homeostasis, and disease.

By defining the mechanisms that regulate inflammasome activity and inflammatory cell death, we aim to uncover fundamental principles governing chronic inflammation and identify new therapeutic opportunities.

2. Intercellular Communication in Tissue Inflammation

Inflammatory responses require coordinated communication between immune cells and surrounding tissues. However, many of the mechanisms that organise inflammation at the tissue level remain poorly understood.

We investigate how macrophages transmit inflammatory information to neighbouring cells, including through CALHM6-dependent ATP signalling and other emerging pathways of intercellular communication.

Our goal is to understand how inflammatory signals propagate through tissues and how communication networks regulate the initiation, amplification, and resolution of inflammation.