Neutrophil Extracellular Traps Induce the Epithelial-Mesenchymal Transition: Implications in Post-COVID-19 Fibrosis

Laura Pandolfi, Sara Bozzini, Vanessa Frangipane, Elena Percivalle, Ada De Luigi, Martina Bruna Violatto, Gianluca Lopez, Elisa Gabanti, Luca Carsana, Maura D’Amato, Monica Morosini, Mara De Amici, Manuela Nebuloni, Tommaso Fossali, Riccardo Colombo, Laura Saracino, Veronica Codullo, Massimiliano Gnecchi, Paolo Bigini, Fausto BaldantiDaniele Lilleri, Federica Meloni

Research output: Contribution to journalArticlepeer-review


The release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19. Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs that correlates with neutrophils count; moreover, the analysis of lung tissues of COVID-19 deceased patients showed a subset of alveolar reactive pneumocytes with a co-expression of epithelial marker and a mesenchymal marker, confirming the induction of EMT mechanism after severe SARS-CoV2 infection. By airway in vitro models, cultivating A549 or 16HBE at air-liquid interface, adding alveolar macrophages (AM), neutrophils and SARS-CoV2, we demonstrated that to trigger a complete EMT expression pattern are necessary the induction of NETosis by SARS-CoV2 and the secretion of AM factors (TGF-β, IL8 and IL1β). All our results highlight the possible mechanism that can induce lung fibrosis after SARS-CoV2 infection.

Original languageEnglish
Article number663303
JournalFrontiers in Immunology
Publication statusPublished - Jun 14 2021


  • COVID-19
  • epithelial-mesenchymal transition
  • lung fibrosis
  • NETosis
  • SARS-CoV2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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