MyCOVID project: Comparison of innate lung responses after ex vivo infection by mycobacteria from the M.tuberculosis complex and the SARSCoV-2

Abstract

International audienceThe recent emergence of the new coronavirus SARS-Cov-2 reminds us of the importance of research on emerging and zoonotic pathogens. Most of the models used to study respiratory pathogens rely on cells lines, which do not represent the diversity of lung cells nor their organization1,2. We validated a model of Precision Cut Lung Slices (PCLS) to study the early steps of infection by Mycobacterium bovis (Mb) and tuberculosis (Mtb), respectively causing bovine and human tuberculosis. While Mb is zoonotic, Mtb is restricted to Humans but host specificities are not understood yet. The bovine PCLS study showed that type I interferon pathway was activated by Mb and not Mtb, with a significant contribution of resident alveolar macrophages3. By adapting the bovine protocol, we used biopsies obtained from surgical resection from lung adenocarcinoma, to obtain human PCLS. This enabled ex vivo infections in a preserved and functional lung micro-environment, with the presence of all resident cell-types and connective tissue architecture.Our project aims to investigate which cell types are infected by SARS-CoV-2, Mb and Mtb; and their contribution to physiopathology and more specifically to the IFN-I pathway, that is key to both antiviral and anti-mycobacterial response. Thus, the MyCOVID project will improve our understanding of the pathophysiology of top two deadliest respiratory diseases worldwide, COVID-19 and tuberculosis