Synthetically rewired macrophages to foster tissue regeneration post virus induced lung damage

• Applicants: Professor Dr. Nico Lachmann; Professorin Dr. Dagmar Wirth
• Subject Area: Immunology ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 524821872

The targeted support of the body's own functions represents a new, attractive strategy for combating disease (referred to as: host-directed therapy, HDT). One focus of HDT is to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology. Among other diseases, bacterial and viral infections of the lung are associated with severe tissue damage, contributing to infection associated lethality and promoting microbial niches. To support tissue regeneration, cell-based immunotherapies with macrophages are of particular interest, as these cells (i) intrinsically provide functions for tissue regeneration and homeostasis, (ii) migrate to damaged tissue and (iii) sense the signals of the tissue environment and can induce pro- or anti-inflammatory responses. In this innovative project we aim to develop a macrophage based HDT strategy that perturbs pathogen-induced hyper-inflammation and reduces exacerbated tissue damage. Using synthetic biology, genetically modified sensor/effector macrophages will be developed that autonomously convert endogenous, infection-associated signals into reliable responses that ultimately lead to tissue regeneration. This strategy will be evaluated for mouse sensor/effector macrophages in the context of pulmonary infection in immunocompetent mice and for human sensor/effector macrophages in advanced in vitro systems as well as in humanized mice.

• DFG Programme: Research Grants