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

• Published in: Frontiers in immunology 2020-09, Vol.11, p.574862
• Main Authors: Motta Junior, Jarbas da Silva, Miggiolaro, Anna Flavia Ribeiro Dos Santos, Nagashima, Seigo, de Paula, Caroline Busatta Vaz, Baena, Cristina Pellegrino, Scharfstein, Julio, de Noronha, Lucia
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Betacoronavirus - immunology; cell-mediated immunity; Coronavirus Infections - immunology; Coronavirus Infections - pathology; Coronavirus Infections - virology; COVID 19; Female; Humans; immune responses; Immunology; Influenza A Virus, H1N1 Subtype - immunology; Influenza, Human - immunology; Influenza, Human - pathology; Influenza, Human - virology; interleukin-4 (IL-4); Interleukin-4 - immunology; Male; mast cells (MC); Mast Cells - immunology; Mast Cells - pathology; Middle Aged; Pandemics; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; Pneumonia, Viral - virology; Proto-Oncogene Proteins c-kit - immunology; Pulmonary Alveoli - immunology; Pulmonary Alveoli - pathology; Pulmonary Alveoli - virology; Pulmonary Edema - immunology; Pulmonary Edema - pathology; Pulmonary Edema - virology; SARS-CoV-2; Thrombosis - immunology; Thrombosis - pathology; Thrombosis - virology
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.574862

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 ( = 6), in contrast to the numbers found in pandemic H1N1-induced pneumonia ( = 10) or Control specimens ( = 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.