Laboratory Tim Lämmermann
Cells of the innate immune response belong to the first responder cells at a local site of inflammation or infection. Upon entry of an infectious organism into the body, these cells mediate a rapid and non-specific immune response to prevent the potential spread of pathogens within the tissue. Unlike the adaptive, specific immune response that develops over days, the early events of the innate immune response occur within hours. When tissues are damaged or infected, cells of the innate immune system undertake within minutes a coordinated, multi-cellular and multi-layered response to isolate sites of tissue damage and microbial invasion from healthy tissue. This immediate immune response is vital to the organism and robust in different inflammatory settings, suggesting in situ safeguard mechanisms on the cellular and molecular level. Phagocytes (neutrophils, macrophages, monocytes) are the major cell types involved in this front line of immune defense and in vitro studies have identified many factors that guide phagocyte migration and regulate their effector functions. While we have learnt from these in vitro studies how defined stimuli can alter immune cell function, we are only starting to discover how phagocytes integrate the plethora of signals arising in inflamed tissues to coordinate their dynamic behavior in physiologically complex in vivo settings.
Our group is interested in how immune cells coordinate and integrate multiple basic cell biological processes (directional sensing, cell polarization, cell adhesion, cell migration, phagocytosis, cell death, cell survival, cell-cell communication) that together shape the dynamic immune response in complex tissue environments. Based on our previous work on the swarm-like behavior of neutrophils in inflamed tissues, we have a particular focus on how phagocytes regulate these processes at the single cell and population levels. To address inter- and intracellular immune cell dynamics under physiologically relevant conditions, we use advanced light microscopy techniques to characterize the behavior of live immune cells in mouse tissues and in vitro models that closely mimic the physiological situation. Our research aims at gathering new insights how innate immune cells (a) sense, detect and eliminate damage in the tissue, (b) communicate with each other for optimal coordination of the innate immune response during wounding, inflammation, infection and anaphylaxis, and (c) strategically position themselves to initiate immune responses. Since most of our models are also applicable to human primary phagocytes, our new insights on the molecular regulation of phagocyte dynamics also promise to contribute new therapeutic strategies to modulate immune responses.