COVID-19 and diabetes mellitus: from pathophysiology to clinical management

Nature Reviews Endocrinology, Journal Year: 2020, Volume and Issue: 17(1), P. 11 - 30

Published: Nov. 13, 2020

Language: Английский

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The burden and risks of emerging complications of diabetes mellitus

Nature Reviews Endocrinology, Journal Year: 2022, Volume and Issue: 18(9), P. 525 - 539

Published: June 6, 2022

Language: Английский

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SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2

Circulation Research, Journal Year: 2021, Volume and Issue: 128(9), P. 1323 - 1326

Published: March 31, 2021

HomeCirculation ResearchVol. 128, No. 9SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2 Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBSARS-CoV-2 Yuyang Lei, Jiao Zhang, Cara R. Schiavon, Ming He, Lili Chen, Hui Shen, Yichi Qian Yin, Yoshitake Cho, Leonardo Andrade, Gerald S. Shadel, Mark Hepokoski, Ting Hongliang Wang, Jin Jason X.-J. Yuan, Atul Malhotra, Uri Manor, Shengpeng Zu-Yi Yuan and John Y-J. Shyy LeiYuyang Lei Cardiology, First Affiliated Hospital Xi'an Jiaotong University (Y.L., Z.-Y.Y.). Cardiovascular Research Center, School Basic Medical Sciences L.C., Q.Y., S.W.). , ZhangJiao Zhang Health Science Center. Department Medicine (Jiao M. H.S., Y.Z., Y.C., J.Y.-J.S.), California, San Diego, La Jolla, CA. SchiavonCara Schiavon https://orcid.org/0000-0002-9311-2145 Waitt Advanced Biophotonics Center (C.R.S., L.A., U.M.). Molecular Cellular Biology Laboratory, Salk Institute for Biological Studies, CA G.S.S.). HeMing He ChenLili Chen ShenHui Shen the Yangzhou (H.S.). ZhangYichi YinQian Yin ChoYoshitake Cho AndradeLeonardo Andrade ShadelGerald Shadel HepokoskiMark Hepokoski Pulmonary, Critical Care Sleep Medicine, (M. J.X.-J.Y., A.M.), LeiTing Pathology, (T.L.), WangHongliang Wang Pathogen Immunology, (H.W.), ZhangJin Pharmacology (Jin Zhang), YuanJason MalhotraAtul Malhotra ManorUri Manor https://orcid.org/0000-0002-9802-1955 WangShengpeng YuanZu-Yi MD, PhD, University, 277 Yanta W Rd, 710061, China, Email E-mail Address: [email protected] ShyyJohn Correspondence to: Shyy, Division 9500 Gilman Dr, 92093, https://orcid.org/0000-0002-5625-753X Originally published31 Mar 2021https://doi.org/10.1161/CIRCRESAHA.121.318902Circulation Research. 2021;128:1323–1326is related toMeet AuthorsOther version(s) this articleYou are viewing most recent version article. Previous versions: March 31, 2021: Ahead Print Meet Author, see p 1239SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection relies on binding S protein (Spike glycoprotein) (angiotensin-converting enzyme) in host cells. Vascular endothelium can be infected by SARS-CoV-2,1 which triggers mitochondrial reactive oxygen species production glycolytic shift.2 Paradoxically, ACE2 is protective cardiovascular system, SARS-CoV-1 promotes lung injury decreasing level lungs.3 In current study, we show that alone damage vascular endothelial cells (ECs) downregulating consequently inhibiting function.We administered a pseudovirus expressing (Pseu-Spike) Syrian hamsters intratracheally. Lung was apparent animals receiving Pseu-Spike, revealed thickening alveolar septa increased infiltration mononuclear (Figure [A]). AMPK (AMP-activated kinase) phosphorylates Ser-680, MDM2 (murine double minute ubiquitinates Lys-788, crosstalk between determines level.4 damaged lungs, levels pAMPK (phospho-AMPK), pACE2 (phospho-ACE2), decreased but those [B], i). Furthermore, complementary phosphorylation eNOS (endothelial NO synthase) Thr-494 Ser-1176 indicated impaired activity. These changes pACE2, ACE2, expression, activity were recapitulated vitro experiments using pulmonary arterial ECs with Pseu-Spike rescued treatment N-acetyl-L-cysteine, inhibitor ii).Download figureDownload PowerPointFigure. SARS-CoV-2 (Severe exacerbates cell (EC) function downregulation impairment.A, Representative H&E histopathology specimens from 8- 12 wk-old male 5-day post administration overexpressing or mock virus control group (n=3 mice per group, 1×108 PFU). Thickened (red arrowhead) arrow). Scale bar=20 μm. B, (n=4) (n=4)–infected hamster lungs subjected Western blot analysis (phospho-AMPK) T172, AMPK, (phospho angiotensin-converting S680, 2, MDM2, peNOS S1176, T494, synthase), β-actin (B, Human EC (PAECs) 24 h without N-acetyl-L-cysteine (NAC; 5 mmol/L) pretreatment h. The extracts analyzed antibodies against proteins as (n=4; ii). C, confocal images morphology treated human recombinant S1 IgG (4 μg/mL) (C, i) adenovirus S680D (ACE2-D) S680L (ACE2-L; 10 MOI) 48 Mitochondria visualized TOM20 antibody (n=4, 50 counted each replicate). bar=2.5 Tubular: majority mitochondria >10 μm length; Intermediate: <≈10 μm; Fragment: spherical (no clear length width). D, Measurement consumption rate (OCR, i iii) extracellular acidification (ECAR, ii iv) ACE2-D vs ACE2-L (10 (n=3) (n=3). E, Real-time quantitative polymerase chain reaction mRNA knock-in mice. Eight-week-old C57BL/6 background used. F, Dose-response curves acetylcholine (ACh, left)- sodium nitroprusside (SNP, right)–mediated relaxation tension phenylephrine (1 μmol/L) precontracted intrapulmonary artery stripes Pseu-Spike-(ACh n=8, SNP n=5) (ACh n=6, virus–infected (1×108 PFU; (n=6) (n=5) (F, animal approved ethical committee University. 2-DG indicates 2-Deoxy-D-glucose; ACE2-D, phospho-mimetic stability; ACE2-L, dephospho-mimetic AMP-activated kinase; AA/R, antimycin A&Rotenone; ENO2, enolase 2; FCCP, carbonyl cyanide-p-(trifluoromethoxy)phenylhydrazone; H&E, Hematoxylin Eosin; HK2, hexokinase HO1, heme oxygenase-1; murine MOI, multiplicity infection; NRF1, nuclear factor 1; peNOS, phospho-eNOS; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3; Resp, respiration; TFAM, transcription A, mitochondrial.We next studied impact function. Confocal fragmentation, indicating altered dynamics [C], To examine whether these due, part, amount overexpressed (ACE2-D, stability) (ACE2-L, stability)4 ECs. As shown Figure ii, had higher number fragmented when compared ACE2-D. Performing assays, found reduced basal respiration, ATP production, maximal respiration [D], Moreover, overexpression caused rate, glucose-induced glycolysis, capacity, reserve Also, incubated attenuated iii iv). We also expressions mitochondria- glycolysis-related genes isolated mice.4 Shown [E], TFAM (mitochondria biogenesis-related genes) increased, whereas ENO2 (glycolysis-related mice, mice.SARS-CoV-2 induces inflammation, leading endotheliitis.1,5 Because bioavailability, examined entry indispensable dysfunctional endothelium. [F], i, endothelium-dependent vasodilation induced arteries Pseu-Spike-administered hamsters, endothelium-independent not affected. acetylcholine- nitroprusside–induced vessels anticipated, acetylcholine-induced hindered comparison There was, however, little difference ACE-L animals.Although use noninfectious limitation our data reveals endothelium, manifested glycolysis. It appears increases redox stress may lead deactivation, upregulation, ultimately destabilization.4 Although findings need confirmed future it seems paradoxical reduction would decrease infectivity, thereby protecting However, dysregulated renin-angiotensin system due exacerbate dysfunction, endotheliitis. Collectively, results suggest protein-exerted overrides infectivity. This conclusion suggests vaccination-generated and/or exogenous only protects infectivity inhibits protein-imposed injury.Nonstandard Abbreviation AcronymsACEangiotensin-converting enzymeECsendothelial cellseNOSendothelial synthasepACE2phospho-ACE2pAMPKphospho-AMPKS proteinSpike glycoproteinData AvailabilityThe support including statistical analyses reagents used, available corresponding author upon request.Sources FundingThis work supported part grants National Natural Foundation China (NSFC) 81870220 (S. Wang), 81800328 (J.Z.), 81941005 (Z.-Y. Yuan); Shaanxi Fund S2020-JC-JQ-0239 Wang); Key Development Program (Grant 2018YFC1311500; Z.-Y. Clinical Award XJTU1AF-CRF-2016-004; Financial support.Disclosures None.Footnotes*Y. J. contributed equally.†U. J.Y.-J. equally senior authors.For Sources Funding Disclosures, page 1324.Correspondence [email protected] [email protected]. Teuwen LA, Geldhof V, Pasut Carmeliet P. COVID-19: vasculature unleashed.Nat Rev Immunol. 2020; 20:389–391. doi: 10.1038/s41577-020-0343-0CrossrefMedlineGoogle Scholar2. Codo AC, Davanzo GG, Monteiro LB, de Souza GF, Muraro SP, Virgilio-da-Silva JV, Prodonoff JS, Carregari VC, Biagi Junior CAO, Crunfli et al. Elevated glucose favor monocyte response through HIF-1α/glycolysis-dependent axis.Cell Metab. 32:437–446.e5. 10.1016/j.cmet.2020.07.007CrossrefMedlineGoogle Scholar3. Kuba K, Imai Y, Rao S, Gao H, Guo Guan Huan Yang P, Deng W, A crucial role angiotensin converting enzyme (ACE2) SARS coronavirus-induced injury.Nat Med. 2005; 11:875–879. 10.1038/nm1267CrossrefMedlineGoogle Scholar4. J, Jain PP, Xiong M, Shi X, Q, Thistlethwaite PA, MDM2-Mediated Ubiquitination contributes development hypertension.Circulation. 142:1190–1204. 10.1161/CIRCULATIONAHA.120.048191LinkGoogle Scholar5. Varga Z, Flammer AJ, Steiger Haberecker Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka Moch H. endotheliitis COVID-19.Lancet. 395:1417–1418. 10.1016/S0140-6736(20)30937-5CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate an article recently published journal forum providing unpublished data. Comments reviewed appropriate tone language. peer-reviewed. Acceptable comments posted website only. issue indexed PubMed. no longer than 500 words will online. References limited 10. Authors cited comment invited reply, appropriate.Comments feedback AHA/ASA Scientific Statements Guidelines directed Manuscript Oversight Committee its page.Sign Submit Response Article Back top Next FiguresReferencesRelatedDetailsCited By Halma Marik P Saleeby Y (2024) Exploring autophagy treating spike protein-related pathology, Endocrine Metabolic Science, 10.1016/j.endmts.2024.100163, 14, (100163), Online publication date: 1-Mar-2024. Zhou L, Wei Sun Lin Li C Glycyrrhizic acid restores downregulated hepatic signaling attenuation mouse steatohepatitis, European Journal Pharmacology, 10.1016/j.ejphar.2024.176365, 967, (176365), Ayyubova G, Gychka Nikolaienko Alghenaim Teramoto T, Shults N Suzuki Role Furin Pathogenesis COVID-19-Associated Neurological Disorders, Life, 10.3390/life14020279, 14:2, (279) Igyártó B Qin Z mRNA-LNP vaccines – good, bad ugly?, Frontiers 10.3389/fimmu.2024.1336906, 15 Zheng Qiu Shu Q Xu J Multifaceted structural injury, 10.3389/fimmu.2024.1332440, Wu Xiang Jing Novakovic V (2023) Damage barriers contribution long COVID, Angiogenesis, 10.1007/s10456-023-09878-5, 27:1, (5-22), 1-Feb-2024. Del Vecchio Balafa O, Dounousi Ekart Fernandez Sarafidis Valdivielso Ferro Mallamaci F COVID-19 disease patients chronic kidney disease, Nephrology Dialysis Transplantation, 10.1093/ndt/gfad170, 39:2, (177-189), 31-Jan-2024. 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Kim Qiao Won I Efficacies S-nitrosoglutathione (GSNO) GSNO reductase 10.3389/fphar.2023.1304697, 14 Monllor Kumar Lloret Ftara Leon Lopez Cervera-Ferri Hackney Multifactorial Causation Alzheimer's Disease Due COVID-19, Disease, 10.3233/JAD-230396, 96:4, (1399-1409) Kuchler Hausinger Braunisch Günthner Wicklein Knier Bleidißel Maier Ribero Lech Adorjan Stubbe Kotilar Heemann U Schmaderer All eyes PCS: retinal microvasculature post-COVID syndrome—study protocol 1 year prospective case–control Archives Psychiatry Neuroscience, 10.1007/s00406-023-01724-5 Fessler Madenspacher Baker Hilligan Bohrer Castro Meacham Johnson McDonald Martin Tucker Mahapatra Cesta Mayer-Barber K Endogenous Therapeutic 25-Hydroxycholesterols May Worsen Early Mice, American Respiratory Cell Biology, 10.1165/rcmb.2023-0007OC, 69:6, (638-648), 1-Dec-2023. Verona Papi anti-SARS-CoV-2 suppresses mithramycin-induced differentiation embryo-fetal erythroleukemia K562 cells, Research, 10.1016/j.yexcr.2023.113853, 433:2, (113853), Shadab Slavin Mahamed Millar Najar Leonard Pietropaoli Dean Fazal Rahman Spleen Tyrosine Kinase VE-cadherin cause barrier disruption Chemistry, 10.1016/j.jbc.2023.105408, 299:12, (105408), Leonhardt Jürgensen Frohme Grajecki Adler Sigal Voll Kruse Körner Eckardt Janssen Gebhardt Schmittner Hippenstiel Witzenrath Suttorp Helbig Lippert Stubbemann Tober-Lau Hillus Haenel Horn Koch Olk Mittermaier Steinbeis Lingscheid Temmesfeld-Wollbrück Zoller Müller-Redetzky Uhrig Grund Ruwwe-Glösenkamp Stegemann Heim Hübner Drosten Corman Opitz Möckel Balzer Spies Weber-Carstens Dang-Heine Hummel Schwanitz Behrens U, Rönnefarth Schmidt Krannich Zvorc Kollek von Kalle Doehn Tabeling Jürgens Kleinschmidt Denker Pfeiffer Pascual-Leone Mrziglod Machleidt Albus Bremer Andermann Garcia Knape Krause Lechtenberg Pergantis Jacobi Ritter Yedikat Pfannkuch Zobel Kellermann Fieberg Jarcy Wetzel Brack Müller-Plathe Zickler Edel Stier Müller Enghard Kretzler Meyer-Arndt Wirsching I, Treue Briesemeister Schlesinger Wendisch Hiller Brumhard Frey Müller-Ide Bauer Thibeault Kurth Sander T Tacke Hepatobiliary long-term consequences dramatically secondary sclerosing cholangitis critically ill patients, Hepatology International, 10.1007/s12072-023-10521-0, 17:6, (1610-1625), Kieser Granoski McClelland Griffiths Bilawchuk Stojic Elawar Jamieson Proud D Marchant Actin cytoskeleton remodeling disrupts physical presents receptors syncytial virus, General Virology, 10.1099/jgv.0.001923, 104:11, 28-Nov-2023. 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Bejoy Williams Cole Manzoor Davoodi Battaile Kaushik Brelidze Effects (ACE2), Biochemistry Biophysics, 10.1016/j.abb.2023.109769, 748, (109769), Thakur Sharma Averbek Liang Pandya Cili Immune landscape imbalance neurological disorders Death 10.1038/s41419-023-06102-6, 14:9 Sullivan Report: Two Reports Pulmonary Hypertension after Vaccination, Diseases, 10.3390/diseases11030114, 11:3, (114) Hsieh Yu Weng serum T-cell immunoglobulin mucin-domain containing molecule 3 systemic inflammation following vaccination, Chinese Association, 10.1097/JCMA.0000000000000969, 86:9, (818-825), 1-Sep-2023. Ke Apolipoprotein viral infection: Risks Mechanisms, Therapy - Nucleic Acids, 10.1016/j.omtn.2023.07.031, 33, (529-542), Silvestri Clemente Moschetti Maioli Carelli Espadas Arias Torelli Longhi De Feo Crosti Sarnicola Salvi Mantovani Arosio Bombaci Pesce Grifantini Abrignani Geginat Muller specific t-cells thyroid enriched acquire tissue-resident memory phenotype, 10.1016/j.clim.2023.109684, 254, (109684), Speer Töllner Benning Bartenschlager Nusshag Kälble Reineke Reichel Schnitzler Zeier Morath Schmitt Bergner Lorenz Schaier BA.1/BA.5 Immunogenicity, Reactogenicity, Activity Vaccination Patients ANCA-Associated Vasculitis: Prospective Observational Cohort Study, Viruses, 10.3390/v15081778, 15:8, (1778) Parry Lefringhausen Turni Neil Cosford Hudson Gillespie 'Spikeopathy': Is Pathogenic, Both Virus Vaccine mRNA, Biomedicines, 10.3390/biomedicines11082287, 11:8, (2287) Dileepan Raveendran Abraham Barua Mast cell-mediated regulation health 10.3389/fmed.2023.1213320, Romero Yue Singla Hamacher Sridhar Moseley Song Mraheil Fischer Zeitlinger Chakraborty Fulton Gan Annex Csanyi Eaton Lucas Direct ENaC activation mitigates vasculopathy SARS-CoV2 protein, 10.3389/fimmu.2023.1241448, Selvaraj Damadarosamy Kiruthiga Rani Duraisamy Dhanasekaran Deruiter Ren Thangavel Parise Evaluation Tuberculo

Language: Английский

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A global view of the interplay between non-alcoholic fatty liver disease and diabetes

The Lancet Diabetes & Endocrinology, Journal Year: 2022, Volume and Issue: 10(4), P. 284 - 296

Published: Feb. 17, 2022

Language: Английский

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Reactive Oxygen Species in Macrophages: Sources and Targets

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 30, 2021

Reactive oxygen species (ROS) are fundamental for macrophages to eliminate invasive microorganisms. However, as observed in nonphagocytic cells, ROS play essential roles processes that different from pathogen killing, signal transduction, differentiation, and gene expression. The outcomes of these events likely depend on the specific subcellular site formation, well duration extent production. While excessive accumulation has long been appreciated its detrimental effects, there is now a deeper understanding their signaling molecules. This could explain failure "all or none" pharmacologic approach with global antioxidants treat several diseases. NADPH oxidase first source identified macrophages. growing evidence highlights mitochondria crucial formation mainly due electron leakage respiratory chain enzymes, such monoamine oxidases. Their role redox signaling, together exact only partially elucidated. Hence, it identify intracellular sources how they influence cellular both physiological pathological conditions develop therapies targeting oxidative networks. In this review, we will focus sites impact metabolic inflammatory highlighting mitochondrial compared non-mitochondrial sources.

Language: Английский

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Lipid droplets fuel SARS-CoV-2 replication and production of inflammatory mediators

PLoS Pathogens, Journal Year: 2020, Volume and Issue: 16(12), P. e1009127 - e1009127

Published: Dec. 16, 2020

Viruses are obligate intracellular parasites that make use of the host metabolic machineries to meet their biosynthetic needs. Thus, identifying pathways essential for virus replication may lead potential targets therapeutic intervention. The mechanisms and explored by SARS-CoV-2 support its within cells not fully known. Lipid droplets (LD) organelles with major functions in lipid metabolism, energy homeostasis transport, have multiple roles infections inflammation. Here we described monocytes from COVID-19 patients an increased LD accumulation compared negative donors. In vitro , infection were seen modulate synthesis uptake as monitored testing CD36, SREBP-1, PPARγ, DGAT-1 expression triggered formation different human cell lines. LDs found close apposition proteins double-stranded (ds)-RNA infected Vero cells. Electron microscopy (EM) analysis show viral particles colocalizing LDs, suggestive might serve assembly platform. Pharmacological modulation inhibition A922500 significantly inhibited well reduced production mediators pro-inflammatory response. Taken together, demonstrate role reprograming pathogenesis, opening new opportunities strategies COVID-19.

Language: Английский

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COVID-19 and Oxidative Stress

Biochemistry (Moscow), Journal Year: 2020, Volume and Issue: 85(12-13), P. 1543 - 1553

Published: Dec. 1, 2020

Pathogenesis of the novel coronavirus infection COVID-19 is subject active research around world. caused by SARS-CoV-2 a complex disease in which interaction virus with target cells, action immune system and body's systemic response to these events are closely intertwined. Many respiratory viral infections, including COVID-19, cause death infected activation innate response, secretion inflammatory cytokines. All processes associated development oxidative stress, makes an important contribution pathogenesis infections. This review analyzes information on stress infections other viruses. The also focuses involvement vascular endothelium pathogenesis.

Language: Английский

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Hypoxia signaling in human health and diseases: implications and prospects for therapeutics

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 7, 2022

Abstract Molecular oxygen (O 2 ) is essential for most biological reactions in mammalian cells. When the intracellular content decreases, it called hypoxia. The process of hypoxia linked to several processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, other stress responses. mechanism underlying cells respond changes mediate subsequent signal response central question during Hypoxia-inducible factors (HIFs) sense regulate expressions a series downstream genes expression, which participate multiple processes cell metabolism, growth/death, proliferation, glycolysis, immune response, tumorigenesis, metastasis. Importantly, signaling also interacts with cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) endoplasmic reticulum (ER) stress. This paper systematically reviews mechanisms activation, control HIF function human health diseases. In addition, therapeutic targets involved balance diseases are summarized highlighted, would provide novel strategies design development drugs.

Language: Английский

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Diabetes, obesity, metabolism, and SARS-CoV-2 infection: the end of the beginning

Cell Metabolism, Journal Year: 2021, Volume and Issue: 33(3), P. 479 - 498

Published: Jan. 22, 2021

Language: Английский

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Monocytes and Macrophages in COVID-19

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: July 21, 2021

COVID-19 is a contagious viral disease caused by SARS-CoV-2 that led to an ongoing pandemic with massive global health and socioeconomic consequences. The characterized primarily, but not exclusively, respiratory clinical manifestations ranging from mild common cold symptoms, including cough fever, severe distress multi-organ failure. Macrophages, heterogeneous group of yolk-sac derived, tissue-resident mononuclear phagocytes complex ontogeny present in all mammalian organs, play critical roles developmental, homeostatic host defense processes tissue-dependent plasticity. In case infection, they are responsible for early pathogen recognition, initiation resolution inflammation, as well repair tissue damage. Monocytes, bone-marrow derived blood-resident phagocytes, recruited under pathological conditions such infections the affected defend organism against invading pathogens aid efficient inflammation. Given their pivotal function potential danger posed dysregulated hyperinflammation, understanding monocyte macrophage phenotypes key tackling disease's mechanisms. Here, we outline current knowledge on monocytes macrophages homeostasis summarize concepts findings role COVID-19. While blood patients moderate inflammatory, interferon-stimulated gene (ISG)-driven phenotype, cellular dysfunction epitomized loss HLA-DR expression induction S100 alarmin dominant feature disease. Pulmonary infiltrating inflammatory hyperactivated state resulting detrimental loop pro-inflammatory cytokine release recruitment cytotoxic effector cells thereby exacerbating damage at site infection.

Language: Английский

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