MotroRepair

Sources of funding

Baillet Latour Biomedical Award (2022-2027, 1 M€)

Summary

Lung tissue repair mechanisms are critical components of the host immune response to respiratory viral infections in order to restore tissue integrity and homeostasis. As a corollary, dysregulated immune responses can be deleterious and substantially contribute to severe disease phenotypes. MotroRepair proposes to investigate the biology of an atypical myeloid cell population emerging during the recovery phase of respiratory viral infections. First, we will perform an in-depth characterization of their transcriptomic, phenotypic and functional profiles in mouse models of respiratory infections. Second, we will investigate their ontogeny and their roles in the orchestration of immune and tissue repair responses. Third, we will characterize their niche and decipher the niche-instructive microenvironmental signals tailoring their identity and functions. Fourth, we will study the influence of chronic stress and host determinants of disease severity on the biology of such myeloid cells and investigate the link between those factors, the dysregulation of their functions and excessive tissue damage and immunopathology. Finally, lung tissue sections of severe Covid-19 patients and age-matched control subjects will be analyzed by multi-colour spectral miscroscopy to illuminate the myeloid spatial landscape of viral-triggered severe disease and assess the existence of such atypical cells in human lungs. MotroRepair is expected to increase our basic understanding of myeloid cell biology and complexity, but also to provide key mechanisms underlying the regulation of host tissue repair responses upon respiratory viral infections, thus providing solid foundations for novel myeloid cell-targeted approaches promoting health and preventing severe disease phenotypes.