Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19
| Autor: | Pranay Dogra, Stuart P. Weisberg, Jing Zhou, Peter A. Sims, Maya M.L. Poon, Anjali Saqi, Steven B. Wells, Joshua I. Gray, Izabela Krupska, Matthew Steinle, Chloé Pasin, Julia Davis-Porada, Donna L. Farber, Rei Matsumoto, Sinead E. Morris, Andrew J. Yates, Matthew R. Baldwin, Michael Chait, Xinzheng V. Guo, Sean Mackay, Thomas J. Connors, Peter A. Szabo, Emma Idzikowski, Amy Ku |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult ARDS Chemokine Myeloid Adolescent T-Lymphocytes tissue resident memory T cells Immunology Inflammation Biology Monocytes Article 03 medical and health sciences Young Adult 0302 clinical medicine Immune system medicine Immunology and Allergy Humans Myeloid Cells Longitudinal Studies Respiratory system Lung lung immunity Aged Aged 80 and over SARS-CoV-2 Age Factors COVID-19 Middle Aged respiratory system medicine.disease macrophages 030104 developmental biology Infectious Diseases medicine.anatomical_structure 030220 oncology & carcinogenesis News And Commentary biology.protein Cytokines medicine.symptom Transcriptome Respiratory tract |
| Zdroj: | Immunity Immunology and Cell Biology |
| ISSN: | 1097-4180 1074-7613 |
| Popis: | Immune response dynamics in COVID-19 and its severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls. In COVID-19 airways, T cells exhibited activated, tissue-resident, and protective profiles; higher T cell frequencies correlated with survival and younger age. Myeloid cells in COVID-19 airways featured hyper-inflammatory signatures and higher frequencies of these cells correlated with mortality and older age. In COVID-19 blood, aberrant CD163+ monocytes predominated over conventional monocytes, and were found in corresponding airway samples and in damaged alveoli. High levels of myeloid chemoattractants in airways suggest recruitment of these cells through a CCL2-CCR2 chemokine axis. Our findings provide insights into immune processes driving COVID-19 lung pathology with therapeutic implications for targeting inflammation in the respiratory tract. Through longitudinal profiling of paired airway and blood from patients with severe COVID-19, Szabo et al. reveal airway immune responses that correlate with age and outcome. They further identify coordinate roles for T and myeloid cells in the respiratory tract and circulation in perpetuating lung pathology and disease pathogenesis. |
| Databáze: | OpenAIRE |
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