Extravascular dynamics and positioning of innate leukocytes and their functional impact for the immune system

• Applicant: Professor Dr. Tim Lämmermann, Ph.D.
• Subject Area: Immunology
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 248768892

Innate immune cells represent the front line of host immune defense at sites of inflammation and infection. Some leukocytes (neutrophils, monocytes) circulate through the bloodstream and only exit the vessel at sites of acute inflammation, whereas other innate cells (macrophages, dendritic cells, mast cells) already reside in peripheral tissues or lymphoid organs. While the choreography of leukocyte extravasation has been extensively studied and refined in mechanistically distinct steps, much less is known about the cascade of events that coordinates innate leukocyte behavior outside the vessel. In vitro studies have identified a huge number of activating cytokines and chemotactic guiding signals for innate immune cells, but we hardly understand where these factors originate from and how they act together to coordinate cellular dynamics in the extravascular space. We know that each innate leukocyte subtype is molecularly distinct and evolved special effector functions. However, we are only starting to understand the basic in vivo mechanisms that enable their specific extravascular tissue positioning, guide their migration paths and foster cellular interactions between them. Further insights into these extravascular events will explain how innate leukocytes mount an efficient immune response during tissue injury, pathogen entry or allergen exposure, and thus restore and ensure health to the organism.The present grant proposal addresses questions of broad importance for the understanding of the dynamic immune response and will aim to investigate how innate immune cells (1) sense, detect and eliminate damage in the tissue, (2) communicate with each other for optimal coordination of the innate immune repsonse during wounding, inflammation and anaphylaxis and (3) strategically position to initiate adaptive immune responses. These studies aim at identifying molecules as potential targets for therapeutic intervention with extravascular leukocyte dynamics and laying the groundwork for targeted therapies to modulate immune responses and ameliorate inflammatory, infectious or anaphylactic conditions.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: low-resolution widefield microscope
• Instrumentation Group: 5000 Labormikroskope