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Poster De Conférence Année : 2023

Comparison of the innate immune response to infection by mycobacteria and SARS-CoV-2 in humans using an ex vivo physiological lung model

Résumé

The recent emergence of the new coronavirus SARS-Cov-2 reminds us 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 tissular organization or cell-cell interactions 1,2. 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. First, we set up the infection conditions (strains, timepoint, detection methods). We validated mycobacteria protocols but faced difficulty with SRAS-Cov-2 detection. We were able to observe infected cells with a neon green recombinant virus. Then we investigated which cell types were infected by our pathogens, by imaging (TEM, confocal microscopy). We focused on alveolar macrophage, a cell which play a key role in the development of both infections. Alveolar macrophages were numerously recruited in infected alveoli 48h after Mtb or Mb infection. The analysis of the transcriptomic signature of infected PCLS is ongoing. Our project will improve our understanding of the pathophysiology of top two deadliest respiratory diseases worldwide, COVID-19 and tuberculosis.
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hal-04161184 , version 1 (13-07-2023)

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  • HAL Id : hal-04161184 , version 1

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Sébastien Eymieux, Aude Remot, Marianne Maquart, Anne Bull- Maurer, Fabienne Arcanger, et al.. Comparison of the innate immune response to infection by mycobacteria and SARS-CoV-2 in humans using an ex vivo physiological lung model. Journées d'animations du réseau RTR FéRI, Jul 2023, Tours, France. ⟨hal-04161184⟩
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