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Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia.
Grant, Rogan A; Morales-Nebreda, Luisa; Markov, Nikolay S; Swaminathan, Suchitra; Querrey, Melissa; Guzman, Estefany R; Abbott, Darryl A; Donnelly, Helen K; Donayre, Alvaro; Goldberg, Isaac A; Klug, Zasu M; Borkowski, Nicole; Lu, Ziyan; Kihshen, Hermon; Politanska, Yuliya; Sichizya, Lango; Kang, Mengjia; Shilatifard, Ali; Qi, Chao; Lomasney, Jon W; Argento, A Christine; Kruser, Jacqueline M; Malsin, Elizabeth S; Pickens, Chiagozie O; Smith, Sean B; Walter, James M; Pawlowski, Anna E; Schneider, Daniel; Nannapaneni, Prasanth; Abdala-Valencia, Hiam; Bharat, Ankit; Gottardi, Cara J; Budinger, G R Scott; Misharin, Alexander V; Singer, Benjamin D; Wunderink, Richard G.
  • Grant RA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Morales-Nebreda L; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Markov NS; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Swaminathan S; Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Querrey M; Robert H. Lurie Comprehensive Cancer Research Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Guzman ER; Division of Thoracic Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Abbott DA; Robert H. Lurie Comprehensive Cancer Research Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Donnelly HK; Robert H. Lurie Comprehensive Cancer Research Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Donayre A; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Goldberg IA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Klug ZM; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Borkowski N; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Lu Z; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Kihshen H; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Politanska Y; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Sichizya L; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Kang M; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Shilatifard A; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Qi C; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Lomasney JW; Simpson Querrey Institute for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Argento AC; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Kruser JM; Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Malsin ES; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Pickens CO; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Smith SB; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Walter JM; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Pawlowski AE; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Schneider D; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Nannapaneni P; Clinical and Translational Sciences Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Abdala-Valencia H; Clinical and Translational Sciences Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Bharat A; Clinical and Translational Sciences Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Gottardi CJ; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Budinger GRS; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Misharin AV; Division of Thoracic Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Singer BD; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Wunderink RG; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. s-buding@northwestern.edu.
Nature ; 590(7847): 635-641, 2021 02.
Article in English | MEDLINE | ID: covidwho-1019856
Semantic information from SemMedBD (by NLM)
1. Pneumonia PROCESS_OF Patients
Subject
Pneumonia
Predicate
PROCESS_OF
Object
Patients
2. Respiratory Distress Syndrom PROCESS_OF C0030705
Subject
Respiratory Distress Syndrom
Predicate
PROCESS_OF
Object
C0030705
3. Tooth Socket LOCATION_OF Virus
Subject
Tooth Socket
Predicate
LOCATION_OF
Object
Virus
4. 2019 novel coronavirus CAUSES Respiratory Failure
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Respiratory Failure
5. Patients LOCATION_OF Bronchoalveolar Lavage Fluid
Subject
Patients
Predicate
LOCATION_OF
Object
Bronchoalveolar Lavage Fluid
6. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
7. Chemotactic Factors PART_OF T-Lymphocyte
Subject
Chemotactic Factors
Predicate
PART_OF
Object
T-Lymphocyte
8. T-Lymphocyte PRODUCES Recombinant Interferon-gamma
Subject
T-Lymphocyte
Predicate
PRODUCES
Object
Recombinant Interferon-gamma
9. Alveolar LOCATION_OF Persistent inflammation
Subject
Alveolar
Predicate
LOCATION_OF
Object
Persistent inflammation
10. 2019 novel coronavirus CAUSES Alveolitis
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Alveolitis
11. Macrophage LOCATION_OF C5203676
Subject
Macrophage
Predicate
LOCATION_OF
Object
C5203676
12. Pneumonia PROCESS_OF Patients
Subject
Pneumonia
Predicate
PROCESS_OF
Object
Patients
13. Respiratory Distress Syndrome, Adult PROCESS_OF Patients
Subject
Respiratory Distress Syndrome, Adult
Predicate
PROCESS_OF
Object
Patients
14. Tooth Socket LOCATION_OF Virus
Subject
Tooth Socket
Predicate
LOCATION_OF
Object
Virus
15. 2019 novel coronavirus CAUSES Respiratory Failure
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Respiratory Failure
16. Patients LOCATION_OF Bronchoalveolar Lavage Fluid
Subject
Patients
Predicate
LOCATION_OF
Object
Bronchoalveolar Lavage Fluid
17. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
18. Chemotactic Factors PART_OF T-Lymphocyte
Subject
Chemotactic Factors
Predicate
PART_OF
Object
T-Lymphocyte
19. T-Lymphocyte PRODUCES Recombinant Interferon-gamma
Subject
T-Lymphocyte
Predicate
PRODUCES
Object
Recombinant Interferon-gamma
20. Alveolar LOCATION_OF Persistent inflammation
Subject
Alveolar
Predicate
LOCATION_OF
Object
Persistent inflammation
21. 2019 novel coronavirus CAUSES Alveolitis
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Alveolitis
22. Macrophages, Alveolar LOCATION_OF 2019 novel coronavirus
Subject
Macrophages, Alveolar
Predicate
LOCATION_OF
Object
2019 novel coronavirus
ABSTRACT
Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia2. Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / T-Lymphocytes / Macrophages, Alveolar / SARS-CoV-2 / COVID-19 Type of study: Etiology study / Incidence study / Observational study / Risk factors Limits: Humans Language: English Journal: Nature Year: 2021 Document Type: Article Affiliation country: S41586-020-03148-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / T-Lymphocytes / Macrophages, Alveolar / SARS-CoV-2 / COVID-19 Type of study: Etiology study / Incidence study / Observational study / Risk factors Limits: Humans Language: English Journal: Nature Year: 2021 Document Type: Article Affiliation country: S41586-020-03148-w