Frontiers in Immunology (Sep 2020)

Mast Cells in Alveolar Septa of COVID-19 Patients: A Pathogenic Pathway That May Link Interstitial Edema to Immunothrombosis

  • Jarbas da Silva Motta Junior,
  • Jarbas da Silva Motta Junior,
  • Anna Flavia Ribeiro dos Santos Miggiolaro,
  • Anna Flavia Ribeiro dos Santos Miggiolaro,
  • Seigo Nagashima,
  • Caroline Busatta Vaz de Paula,
  • Cristina Pellegrino Baena,
  • Cristina Pellegrino Baena,
  • Julio Scharfstein,
  • Lucia de Noronha

DOI
https://doi.org/10.3389/fimmu.2020.574862
Journal volume & issue
Vol. 11

Abstract

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It is currently believed that innate immunity is unable to prevent the spread of SARS-CoV-2 from the upper airways to the alveoli of high-risk groups of patients. SARS-CoV-2 replication in ACE-2-expressing pneumocytes can drive the diffuse alveolar injury through the cytokine storm and immunothrombosis by upregulating the transcription of chemokine/cytokines, unlike several other respiratory viruses. Here we report histopathology data obtained in post-mortem lung biopsies of COVID-19, showing the increased density of perivascular and septal mast cells (MCs) and IL-4-expressing cells (n = 6), in contrast to the numbers found in pandemic H1N1-induced pneumonia (n = 10) or Control specimens (n = 10). Noteworthy, COVID-19 lung biopsies showed a higher density of CD117+ cells, suggesting that c-kit positive MCs progenitors were recruited earlier to the alveolar septa. These findings suggest that MC proliferation/differentiation in the alveolar septa might be harnessed by the shift toward IL-4 expression in the inflamed alveolar septa. Future studies may clarify whether the fibrin-dependent generation of the hyaline membrane, processes that require the diffusion of procoagulative plasma factors into the alveolar lumen and the endothelial dysfunction, are preceded by MC-driven formation of interstitial edema in the alveolar septa.

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