Inflammasome activation in infected macrophages drives COVID-19 pathology.

Angiotensin-Converting Enzyme 2 Animals COVID-19 / pathology Humans Inflammasomes / metabolism Interleukin-1 Interleukin-18 Lung / pathology Macrophages / metabolism Mice NLR Family, Pyrin Domain-Containing 3 Protein / metabolism Pneumonia / metabolism Pyroptosis Receptors, IgG SARS-CoV-2 / metabolism

Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
06 2022
Historique:
received: 30 07 2021
accepted: 25 04 2022
pubmed: 29 4 2022
medline: 18 6 2022
entrez: 28 4 2022
Statut: ppublish

Résumé

Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA and a sustained interferon (IFN) response, all of which are recapitulated and required for pathology in the SARS-CoV-2-infected MISTRG6-hACE2 humanized mouse model of COVID-19, which has a human immune system

Identifiants

DOI: 10.1038/s41586-022-04802-1 PMID: 35483404 PMC: PMC9288243
pubmed: 35483404
doi: 10.1038/s41586-022-04802-1
pii: 10.1038/s41586-022-04802-1
pmc: PMC9288243
mid: NIHMS1809392
doi:

Substances chimiques

Inflammasomes 0
Interleukin-1 0
Interleukin-18 0
NLR Family, Pyrin Domain-Containing 3 Protein 0
Receptors, IgG 0
Angiotensin-Converting Enzyme 2 EC 3.4.17.23

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

585-593

Subventions

Organisme : Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation)
ID : DRG-2316-18
Organisme : NIAID NIH HHS
ID : T32 AI007517
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : Howard Hughes Medical Institute (HHMI)
ID : HHMI Investigator
Organisme : Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)
ID : R01AI157488
Organisme : NIAID NIH HHS
ID : R01 AI118855
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK106857
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : GM131642
Organisme : NIAID NIH HHS
ID : P01 AI061093
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA239444
Pays : United States
Organisme : NIAID NIH HHS
ID : K08 AI128043
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA260507
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM135928
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM131642
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics)
ID : CA016359
Organisme : Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)
ID : 2T32AI007517
Organisme : NIGMS NIH HHS
ID : R35 GM142687
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI157488
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016359
Pays : United States
Organisme : Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)
ID : AI118855
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : GM135928
Organisme : Howard Hughes Medical Institute
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Gaebler, C. et al. Evolution of antibody immunity to SARS-CoV-2. Nature 591, 639–644 (2021).
doi: 10.1038/s41586-021-03207-w pubmed: 33461210 pmcid: 8221082
Acharya, D., Liu, G. & Gack, M. U. Dysregulation of type I interferon responses in COVID-19. Nat. Rev. Immunol. 20, 397–398 (2020).
doi: 10.1038/s41577-020-0346-x pubmed: 32457522 pmcid: 7249038
Pairo-Castineira, E. et al. Genetic mechanisms of critical illness in COVID-19. Nature 591, 92–98 (2020).
Nienhold, R. et al. Two distinct immunopathological profiles in autopsy lungs of COVID-19. Nat. Commun. 11, 5086 (2020).
doi: 10.1038/s41467-020-18854-2 pubmed: 33033248 pmcid: 7546638
Zhou, Z. et al. Heightened innate immune responses in the respiratory tract of COVID-19 patients. Cell Host Microbe 27, 883–890 (2020).
Dolan, M. E. et al. Investigation of COVID-19 comorbidities reveals genes and pathways coincident with the SARS-CoV-2 viral disease. Sci. Rep. 10, 20848 (2020).
doi: 10.1038/s41598-020-77632-8 pubmed: 33257774 pmcid: 7704638
Delorey, T. M. et al. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature 595, 107–113 (2021).
doi: 10.1038/s41586-021-03570-8 pubmed: 33915569 pmcid: 8919505
Singanayagam, A. et al. Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020. Euro Surveill. 25, 2001483 (2020).
doi: 10.2807/1560-7917.ES.2020.25.32.2001483 pmcid: 7427302
Decker, A. et al. Prolonged SARS-CoV-2 shedding and mild course of COVID-19 in a patient after recent heart transplantation. Am. J. Transplant. 20, 3239–3245 (2020).
doi: 10.1111/ajt.16133 pubmed: 32519406
Jeong, H. W. et al. Viable SARS-CoV-2 in various specimens from COVID-19 patients. Clin. Microbiol. Infect. 26, 1520–1524 (2020).
doi: 10.1016/j.cmi.2020.07.020 pubmed: 32711057 pmcid: 7375961
Liu, W. D. et al. Prolonged virus shedding even after seroconversion in a patient with COVID-19. J. Infect. 81, 318–356 (2020).
pubmed: 32283159 pmcid: 7151318
van Kampen, J. J. A. et al. Duration and key determinants of infectious virus shedding in hospitalized patients with coronavirus disease-2019 (COVID-19). Nat. Commun. 12, 267 (2021).
doi: 10.1038/s41467-020-20568-4 pubmed: 33431879 pmcid: 7801729
Folgueira, M. D., Luczkowiak, J., Lasala, F., Perez-Rivilla, A. & Delgado, R. Prolonged SARS-CoV-2 cell culture replication in respiratory samples from patients with severe COVID-19. Clin. Microbiol. Infect. 27, 886–891 (2021).
doi: 10.1016/j.cmi.2021.02.014 pubmed: 33631334 pmcid: 7898982
Lucas, C. et al. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 584, 463–469 (2020).
doi: 10.1038/s41586-020-2588-y pubmed: 32717743 pmcid: 7477538
Del Valle, D. M. et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat. Med. 26, 1636–1643 (2020).
doi: 10.1038/s41591-020-1051-9 pubmed: 32839624 pmcid: 7869028
Wu, C. et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern. Med. 180, 934–943 (2020).
doi: 10.1001/jamainternmed.2020.0994 pubmed: 32167524
Rodrigues, T. S. et al. Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J. Exp. Med. 218, e20201707 (2021).
doi: 10.1084/jem.20201707 pubmed: 33231615
Henry, B. M. et al. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: a pooled analysis. Am. J. Emerg. Med. 38, 1722–1726 (2020).
doi: 10.1016/j.ajem.2020.05.073 pubmed: 32738466 pmcid: 7251362
Sefik, E. et al. A humanized mouse model of chronic COVID-19. Nat. Biotechnol. https://doi.org/10.1038/s41587-021-01155-4 (2021).
Grant, R. A. et al. Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia. Nature 590, 635–641 (2021).
Beigel, J. H. et al. Remdesivir for the treatment of COVID-19—final report. N. Engl. J. Med. 383, 1813–1826 (2020).
doi: 10.1056/NEJMoa2007764 pubmed: 32445440
Pruijssers, A. J. et al. Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice. Cell Rep. 32, 107940 (2020).
doi: 10.1016/j.celrep.2020.107940 pubmed: 32668216 pmcid: 7340027
Yin, W. et al. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science 368, 1499–1504 (2020).
doi: 10.1126/science.abc1560 pubmed: 32358203 pmcid: 7199908
Havervall, S. et al. Symptoms and functional impairment assessed 8 months after mild COVID-19 among health care workers. JAMA 325, 2015–2016 (2021).
doi: 10.1001/jama.2021.5612 pubmed: 33825846 pmcid: 8027932
Nasserie, T., Hittle, M. & Goodman, S. N. Assessment of the frequency and variety of persistent symptoms among patients with COVID-19: a systematic review. JAMA Netw. Open 4, e2111417 (2021).
doi: 10.1001/jamanetworkopen.2021.11417 pubmed: 34037731 pmcid: 8155823
Ginestra, J. C., Mitchell, O. J. L., Anesi, G. L. & Christie, J. D. COVID-19 critical illness: a data-driven review. Annu. Rev. Med. 73, 95–111 (2022).
doi: 10.1146/annurev-med-042420-110629 pubmed: 34520220
Phetsouphanh, C. et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat. Immunol. 23, 210–216 (2022).
doi: 10.1038/s41590-021-01113-x pubmed: 35027728
Basile, K. et al. Cell-based culture of SARS-CoV-2 informs infectivity and safe de-isolation assessments during COVID-19. Clin. Infect. Dis. https://doi.org/10.1093/cid/ciaa1579 (2020).
Vora, S. M., Lieberman, J. & Wu, H. Inflammasome activation at the crux of severe COVID-19. Nat. Rev. Immunol. 21, 694–703 (2021).
doi: 10.1038/s41577-021-00588-x pubmed: 34373622 pmcid: 8351223
Major, J. et al. Type I and III interferons disrupt lung epithelial repair during recovery from viral infection. Science 369, 712–717 (2020).
doi: 10.1126/science.abc2061 pubmed: 32527928 pmcid: 7292500
The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19—preliminary report. N. Engl. J. Med. 384, 693–704 (2020).
Polak, S. B., Van Gool, I. C., Cohen, D., von der Thusen, J. H. & van Paassen, J. A systematic review of pathological findings in COVID-19: a pathophysiological timeline and possible mechanisms of disease progression. Mod. Pathol. 33, 2128–2138 (2020).
doi: 10.1038/s41379-020-0603-3 pubmed: 32572155 pmcid: 7306927
Tian, S. et al. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies. Mod. Pathol. 33, 1007–1014 (2020).
Menter, T. et al. Postmortem examination of COVID‐19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology 77, 198–209 (2020).
doi: 10.1111/his.14134 pubmed: 32364264 pmcid: 7496150
Barton, L. M., Duval, E. J., Stroberg, E., Ghosh, S. & Mukhopadhyay, S. Covid-19 autopsies, Oklahoma, USA. Am. J. Clin. Pathol. 153, 725–733 (2020).
doi: 10.1093/ajcp/aqaa062 pubmed: 32275742
Xu, Z. et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 8, 420–422 (2020).
doi: 10.1016/S2213-2600(20)30076-X pubmed: 32085846 pmcid: 7164771
Strunz, M. et al. Alveolar regeneration through a Krt8
doi: 10.1038/s41467-020-17358-3 pubmed: 32678092 pmcid: 7366678
Kobayashi, Y. et al. Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis. Nat. Cell Biol. 22, 934–946 (2020).
doi: 10.1038/s41556-020-0542-8 pubmed: 32661339 pmcid: 7461628
Choi, J. et al. Inflammatory signals induce AT2 cell-derived damage-associated transient progenitors that mediate alveolar regeneration. Cell Stem Cell 27, 366–382 e367 (2020).
doi: 10.1016/j.stem.2020.06.020 pubmed: 32750316 pmcid: 7487779
Wolfel, R. et al. Virological assessment of hospitalized patients with COVID-2019. Nature 581, 465–469 (2020).
doi: 10.1038/s41586-020-2196-x pubmed: 32235945
Xie, X. et al. An infectious cDNA clone of SARS-CoV-2. Cell Host Microbe 27, 841–848 (2020).
doi: 10.1016/j.chom.2020.04.004 pubmed: 32289263 pmcid: 7153529
Hassan, A. et al. A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies. Cell. 182, 744–753 (2020).
doi: 10.1016/j.cell.2020.06.011 pubmed: 32553273 pmcid: 7284254
Muus, C. et al. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat. Med. 27, 546–559 (2021).
doi: 10.1038/s41591-020-01227-z pubmed: 33654293
Bournazos, S., Gupta, A. & Ravetch, J. V. The role of IgG Fc receptors in antibody-dependent enhancement. Nat. Rev. Immunol. 20, 633–643 (2020).
doi: 10.1038/s41577-020-00410-0 pubmed: 32782358
Davide, F. R. et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 584, 437–442 (2020).
Bournazos, S. & Ravetch, J. V. Fcγ receptor function and the design of vaccination strategies. Immunity 47, 224–233 (2017).
doi: 10.1016/j.immuni.2017.07.009 pubmed: 28813656 pmcid: 5573140
Chakraborty, S. et al. Proinflammatory IgG Fc structures in patients with severe COVID-19. Nat. Immunol. 22, 67–73 (2021).
doi: 10.1038/s41590-020-00828-7 pubmed: 33169014
Hoepel, W. et al. High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages. Sci. Transl. Med. 13, eabf8654 (2021).
doi: 10.1126/scitranslmed.abf8654 pubmed: 33979301
Larsen, M. D. et al. Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity. Science 371, eabc8378 (2021).
doi: 10.1126/science.abc8378 pubmed: 33361116
Evren, E. et al. Distinct developmental pathways from blood monocytes generate human lung macrophage diversity. Immunity 54, 259–275 (2021).
doi: 10.1016/j.immuni.2020.12.003 pubmed: 33382972
Hadjadj, J. et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 369, 718–724 (2020).
doi: 10.1126/science.abc6027 pubmed: 32661059 pmcid: 7402632
Chua, R. L. et al. COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. Nat. Biotechnol. 38, 970–979 (2020).
doi: 10.1038/s41587-020-0602-4 pubmed: 32591762
Lei, X. et al. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun. 11, 3810 (2020).
doi: 10.1038/s41467-020-17665-9 pubmed: 32733001 pmcid: 7392898
Zhang, J. Y. et al. Single-cell landscape of immunological responses in patients with COVID-19. Nat. Immunol. 21, 1107–1118 (2020).
doi: 10.1038/s41590-020-0762-x pubmed: 32788748
Allen, I. C. et al. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30, 556–565 (2009).
doi: 10.1016/j.immuni.2009.02.005 pubmed: 19362020 pmcid: 2803103
Thomas, P. G. et al. The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1. Immunity 30, 566–575 (2009).
doi: 10.1016/j.immuni.2009.02.006 pubmed: 19362023 pmcid: 2765464
Pothlichet, J. et al. Type I IFN triggers RIG-I/TLR3/NLRP3-dependent inflammasome activation in influenza A virus infected cells. PLoS Pathog. 9, e1003256 (2013).
doi: 10.1371/journal.ppat.1003256 pubmed: 23592984 pmcid: 3623797
Ferreira, A. C. et al. SARS-CoV-2 engages inflammasome and pyroptosis in human primary monocytes. Cell Death Discov. 7, 43 (2021).
doi: 10.1038/s41420-021-00428-w pubmed: 33649297 pmcid: 7919254
Pan, P. et al. SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nat. Commun. 12, 4664 (2021).
doi: 10.1038/s41467-021-25015-6 pubmed: 34341353 pmcid: 8329225
Xu, H. et al. SARS-CoV-2 viroporin encoded by ORF3a triggers the NLRP3 inflammatory pathway. Virology 568, 13–22 (2022).
doi: 10.1016/j.virol.2022.01.003 pubmed: 35066302
Zhao, J. et al. Detection of differentially abundant cell subpopulations in scRNA-seq data. Proc. Natl Acad. Sci. USA 118, e2100293118 (2021).
doi: 10.1073/pnas.2100293118 pubmed: 34001664 pmcid: 8179149
Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 1888–1902 (2019).
doi: 10.1016/j.cell.2019.05.031 pubmed: 31178118 pmcid: 6687398
Corman, V. M. et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 25, 2000045 (2020).
pmcid: 6988269
Schäfer, A. et al. Antibody potency, effector function, and combinations in protection and therapy for SARS-CoV-2 infection in vivo. J. Exp. Med. 218, e20201993 (2020).
Yu, H. et al. A novel humanized mouse model with significant improvement of class-switched, antigen-specific antibody production. Blood 129, 959–969 (2017).
doi: 10.1182/blood-2016-04-709584 pubmed: 28077418 pmcid: 5324713
Rongvaux, A. et al. Development and function of human innate immune cells in a humanized mouse model. Nat. Biotechnol. 32, 364–372 (2014).
doi: 10.1038/nbt.2858 pubmed: 24633240 pmcid: 4017589
Israelow, B. et al. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. J. Exp. Med. 217, e20201241 (2020).
doi: 10.1084/jem.20201241 pubmed: 32750141 pmcid: 7401025
Coll, R. C. et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med. 21, 248–255 (2015).
doi: 10.1038/nm.3806 pubmed: 25686105 pmcid: 4392179
Perera, A. P. et al. MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice. Sci. Rep. 8, 8618 (2018).
doi: 10.1038/s41598-018-26775-w pubmed: 29872077 pmcid: 5988655
Dixon, K. O. et al. TIM-3 restrains anti-tumour immunity by regulating inflammasome activation. Nature 595, 101–106 (2021).
doi: 10.1038/s41586-021-03626-9 pubmed: 34108686 pmcid: 8627694
Wei, J. et al. Genome-wide CRISPR screens reveal host factors critical for SARS-CoV-2 infection. Cell 184, 76–91 (2020).
Sun, F., Xiao, G. & Qu, Z. Murine bronchoalveolar lavage. Bio Protoc. 7, e2287 (2017).
pubmed: 29082285 pmcid: 5659634
Stack, J. H. et al. IL-converting enzyme/caspase-1 inhibitor VX-765 blocks the hypersensitive response to an inflammatory stimulus in monocytes from familial cold autoinflammatory syndrome patients. J. Immunol. 175, 2630–2634 (2005).
doi: 10.4049/jimmunol.175.4.2630 pubmed: 16081838
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
doi: 10.1093/bioinformatics/bts635 pubmed: 23104886
Anders, S., Pyl, P. T. & Huber, W. HTSeq-a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).
doi: 10.1093/bioinformatics/btu638 pubmed: 25260700
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
doi: 10.1186/s13059-014-0550-8 pubmed: 25516281 pmcid: 4302049

Auteurs

Esen Sefik (E)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
ORCID: 0000-0002-6807-3498

Rihao Qu (R)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Computational Biology and Bioinformatics Program, Yale University, New Haven, CT, USA.

Caroline Junqueira (C)

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil.
ORCID: 0000-0003-0545-0986

Eleanna Kaffe (E)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.

Haris Mirza (H)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.

Jun Zhao (J)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.

J Richard Brewer (JR)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.

Ailin Han (A)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.

Holly R Steach (HR)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
ORCID: 0000-0003-0018-3129

Benjamin Israelow (B)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
ORCID: 0000-0002-1308-8246

Holly N Blackburn (HN)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.

Sofia E Velazquez (SE)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
ORCID: 0000-0001-5954-3518

Y Grace Chen (YG)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
ORCID: 0000-0003-3574-5734

Stephanie Halene (S)

Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Section of Hematology, Yale Cancer Center and Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
ORCID: 0000-0002-2737-9810

Akiko Iwasaki (A)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA.
ORCID: 0000-0002-7824-9856

Eric Meffre (E)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
ORCID: 0000-0003-4326-0171

Michel Nussenzweig (M)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA.
Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.
ORCID: 0000-0003-0592-8564

Judy Lieberman (J)

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-6200-4715

Craig B Wilen (CB)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.
ORCID: 0000-0003-2495-9403

Yuval Kluger (Y)

Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Program of Applied Mathematics, Yale University, New Haven, CT, USA.
ORCID: 0000-0002-3035-071X

Richard A Flavell (RA)

Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. Richard.Flavell@yale.edu.
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA. Richard.Flavell@yale.edu.
ORCID: 0000-0003-4461-0778

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Exopeptidases › Carboxypeptidases › Angiotensin-converting enzyme 2 › Inflammasome activation in infected...
questionsmedicales.fr › Eucaryotes › Animaux › Inflammasome activation in infected...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Inflammasome activation in infected...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Inflammasome activation in infected...
questionsmedicales.fr › Structures macromoléculaires › Complexes multiprotéiques › Inflammasomes › Inflammasome activation in infected...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Monokines › Interleukine-1 › Inflammasome activation in infected...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-18 › Inflammasome activation in infected...
questionsmedicales.fr › Appareil respiratoire › Poumon › Inflammasome activation in infected...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Inflammasome activation in infected...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Inflammasome activation in infected...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Protéines NLR › Protéine-3 de la famille des NLR contenant un domaine pyrine › Inflammasome activation in infected...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Inflammasome activation in infected...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Pyroptose › Inflammasome activation in infected...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteur Fc › Récepteurs du fragment Fc des IgG › Inflammasome activation in infected...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Inflammasome activation in infected...