Monocyte subset redistribution from blood to kidneys in patients with Puumala virus caused hemorrhagic fever with renal syndrome.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
06
10
2020
accepted:
17
02
2021
revised:
22
03
2021
pubmed:
11
3
2021
medline:
27
7
2021
entrez:
10
3
2021
Statut:
epublish
Résumé
Innate immune cells like monocytes patrol the vasculature and mucosal surfaces, recognize pathogens, rapidly redistribute to affected tissues and cause inflammation by secretion of cytokines. We previously showed that monocytes are reduced in blood but accumulate in the airways of patients with Puumala virus (PUUV) caused hemorrhagic fever with renal syndrome (HFRS). However, the dynamics of monocyte infiltration to the kidneys during HFRS, and its impact on disease severity are currently unknown. Here, we examined longitudinal peripheral blood samples and renal biopsies from HFRS patients and performed in vitro experiments to investigate the fate of monocytes during HFRS. During the early stages of HFRS, circulating CD14-CD16+ nonclassical monocytes (NCMs) that patrol the vasculature were reduced in most patients. Instead, CD14+CD16- classical (CMs) and CD14+CD16+ intermediate monocytes (IMs) were increased in blood, in particular in HFRS patients with more severe disease. Blood monocytes from patients with acute HFRS expressed higher levels of HLA-DR, the endothelial adhesion marker CD62L and the chemokine receptors CCR7 and CCR2, as compared to convalescence, suggesting monocyte activation and migration to peripheral tissues during acute HFRS. Supporting this hypothesis, increased numbers of HLA-DR+, CD14+, CD16+ and CD68+ cells were observed in the renal tissues of acute HFRS patients compared to controls. In vitro, blood CD16+ monocytes upregulated CD62L after direct exposure to PUUV whereas CD16- monocytes upregulated CCR7 after contact with PUUV-infected endothelial cells, suggesting differential mechanisms of activation and response between monocyte subsets. Together, our findings suggest that NCMs are reduced in blood, potentially via CD62L-mediated attachment to endothelial cells and monocytes are recruited to the kidneys during HFRS. Monocyte mobilization, activation and functional impairment together may influence the severity of disease in acute PUUV-HFRS.
Identifiants
pubmed: 33690725
doi: 10.1371/journal.ppat.1009400
pii: PPATHOGENS-D-20-02196
pmc: PMC7984619
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009400Commentaires et corrections
Type : ErratumIn
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Nat Immunol. 2006 Mar;7(3):311-7
pubmed: 16462739
Infect Dis (Lond). 2016 Sep;48(9):682-7
pubmed: 27299174
J Neuroimmunol. 2016 Jun 15;295-296:12-7
pubmed: 27235343
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13837-42
pubmed: 12368479
Clin Immunol Immunopathol. 1996 Jan;78(1):47-55
pubmed: 8599883
Nat Rev Immunol. 2015 Nov;15(11):692-704
pubmed: 26471775
Virus Res. 2018 Jul 15;253:92-102
pubmed: 29857122
Front Microbiol. 2014 Dec 22;5:727
pubmed: 25566236
Viruses. 2014 May 26;6(5):2214-41
pubmed: 24859344
Front Microbiol. 2015 Jan 05;5:733
pubmed: 25601858
J Interferon Cytokine Res. 2009 Jun;29(6):313-26
pubmed: 19441883
J Med Virol. 2018 Jun;90(6):1003-1009
pubmed: 29446472
Immunol Rev. 2019 May;289(1):9-30
pubmed: 30977202
Immunol Lett. 2007 Nov 15;113(2):117-20
pubmed: 17897725
J Clin Microbiol. 2007 Aug;45(8):2491-7
pubmed: 17537944
J Infect Dis. 2016 Oct 15;214(suppl 3):S275-S280
pubmed: 27521367
J Clin Microbiol. 2016 May;54(5):1335-9
pubmed: 26962084
Front Immunol. 2017 May 18;8:567
pubmed: 28572804
Nat Rev Immunol. 2008 May;8(5):362-71
pubmed: 18379575
Int J Infect Dis. 2017 Oct;63:88-94
pubmed: 28804005
Science. 1993 Oct 15;262(5132):436-8
pubmed: 7692600
Oncoimmunology. 2016 May 24;5(8):e1189052
pubmed: 27622061
PLoS Pathog. 2011 Jun;7(6):e1002105
pubmed: 21731495
BMC Infect Dis. 2013 Oct 28;13:501
pubmed: 24160911
Front Immunol. 2019 Jul 26;10:1761
pubmed: 31402918
Circ Res. 2011 Aug 5;109(4):374-81
pubmed: 21680896
Nat Immunol. 2016 Nov;17(11):1263-1272
pubmed: 27668800
Front Cell Infect Microbiol. 2020 Jun 12;10:281
pubmed: 32596167
Viruses. 2019 Jul 24;11(8):
pubmed: 31344894
Mol Immunol. 2009 Aug;46(13):2682-93
pubmed: 19545899
Clin Microbiol Rev. 2010 Apr;23(2):412-41
pubmed: 20375360
PLoS One. 2015 Nov 11;10(11):e0142872
pubmed: 26561052
Cell Host Microbe. 2014 Jul 9;16(1):115-27
pubmed: 24981333
Immunity. 2010 Sep 24;33(3):375-86
pubmed: 20832340
J Virol. 2017 Apr 28;91(10):
pubmed: 28356527
PLoS Pathog. 2017 Jun 22;13(6):e1006462
pubmed: 28640917
BMC Immunol. 2011 Nov 16;12:65
pubmed: 22085404
J Infect Dis. 2002 Sep 15;186(6):843-6
pubmed: 12198621
Nat Rev Microbiol. 2013 Aug;11(8):539-50
pubmed: 24020072
Int J Biochem Cell Biol. 2004 Oct;36(10):1882-6
pubmed: 15203102
PLoS Pathog. 2014 Nov 20;10(11):e1004521
pubmed: 25412359
J Immunol Res. 2017;2017:6104054
pubmed: 28316998
Tissue Barriers. 2015 Apr 03;3(1-2):e978720
pubmed: 25838983
Eur J Clin Microbiol Infect Dis. 2010 Dec;29(12):1507-11
pubmed: 20725844
Immunity. 2018 Oct 16;49(4):595-613
pubmed: 30332628
J Infect Dis. 2019 May 5;219(11):1832-1840
pubmed: 30698699
Science. 2007 Aug 3;317(5838):666-70
pubmed: 17673663
Blood. 2011 Sep 22;118(12):e50-61
pubmed: 21803849
J Clin Virol. 2015 Mar;64:128-36
pubmed: 25453325
Front Immunol. 2018 Sep 18;9:2098
pubmed: 30283445
J Intern Med. 2019 May;285(5):510-523
pubmed: 30663801
Viruses. 2020 Apr 17;12(4):
pubmed: 32316667