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Research Focus

Our research concentrates on the innate immune response to infections, focusing specifically on the comprehensive repertoire of macrophage functions in development, health and disease. We study the initiation and resolution of clinically relevant infections, and the role of danger molecules and their interactions with host structures and pathways. Our latest research is directed towards the interplay of immune cells in regulating tissue homeostasis in health and disease.

Innate immunity, the evolutionarily conserved arm of the immune system, is instrumental in maintaining tissue homeostasis while at the same time providing the tools to immediately sense and respond to danger signals such as invading pathogens, metabolic stress or injuries. This wide and diverse range of tasks requires an incredible plasticity and flexibility of the players involved, with tissue-resident macrophages being essential in orchestrating many of these responses.

Using clinically relevant infection, injury and metabolic stress models, research in the Knapp-Lab is focusing on how host factors can influence the balance of innate responses in steady state and upon danger.

Host-pathogen interplay

Dysregulations in the balance of innate immune mechanisms can profoundly alter the susceptibility to bacterial and viral infections, and predispose to chronic diseases. A prime example of dysregulated immune homeostasis occurs following viral lung infections or acute lung injury, which are the medically most important risk factors for secondary bacterial pneumonia. We focus on how host factors impact pulmonary immune homeostasis in an attempt to identify immune-modulatory mechanisms that can be used to maintain tissue homeostasis and thus prevent secondary infections.

Inflammation

Using systems approaches, the Knapp-Lab aims to unravel temporal response patterns in a given tissue upon infection in order to understand the long-term effects of disrupted homeostasis herein. In a second line of research we investigate how perturbed homeostasis in the course of inflammatory or inherited disorders impacts the functionality of immune effector cells, thus affecting the outcome of common infectious diseases such as Gram-negative sepsis or pneumonia.

Macrophages

A central question addressed by the Knapp-Lab pertains to the huge functional repertoire of tissue-resident macrophages. As such, we study how alveolar macrophages, the tissue-resident macrophage subset in the lungs, exert their pleiotropic functions upon danger, and explore the forces that maintain these cells in a de-activated phenotype at homeostasis. We have identified several players that importantly shape alveolar macrophage functionality and demonstrated their relevance in various infection models.