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M1-like macrophages are potent producers of anti-viral interferons and M1-associated marker-positive lung macrophages are decreased during rhinovirus-induced asthma exacerbations

Title: M1-like macrophages are potent producers of anti-viral interferons and M1-associated marker-positive lung macrophages are decreased during rhinovirus-induced asthma exacerbations
Authors: Nikonova, A
Khaitov, M
Jackson, DJ
Traub, S
Trujillo-Torralbo, M-B
Kudlay, DA
Dvornikov, AS
Del-Rosario, A
Valenta, R
Stanciu, LA
Khaitov, R
Johnston, SL
Item Type: Journal Article
Abstract: Background Macrophages (Mф) can be M1/M2 polarized by Th1/2 signals, respectively. M2-like Mф are thought to be important in asthma pathogenesis, and M1-like in anti-infective immunity, however their roles in virus-induced asthma exacerbations are unknown. Our objectives were (i) to assess polarised Mф phenotype responses to rhinovirus (RV) infection in vitro and (ii) to assess Mф phenotypes in healthy subjects and people with asthma before and during experimental RV infection in vivo. Methods We investigated characteristics of polarized/unpolarized human monocyte-derived Mф (MDM, from 3–6 independent donors) in vitro and evaluated frequencies of M1/M2-like bronchoalveolar lavage (BAL) Mф in experimental RV-induced asthma exacerbation in 7 healthy controls and 17 (at baseline) and 18 (at day 4 post infection) people with asthma. Findings We observed in vitro: M1-like but not M2-like or unpolarized MDM are potent producers of type I and III interferons in response to RV infection (P<0.0001), and M1-like are more resistant to RV infection (P<0.05); compared to M1-like, M2-like MDM constitutively produced higher levels of CCL22/MDC (P = 0.007) and CCL17/TARC (P<0.0001); RV-infected M1-like MDM were characterized as CD14+CD80+CD197+ (P = 0.002 vs M2-like, P<0.0001 vs unpolarized MDM). In vivo we found reduced percentages of M1-like CD14+CD80+CD197+ BAL Mф in asthma during experimental RV16 infection compared to baseline (P = 0.024). Interpretation Human M1-like BAL Mф are likely important contributors to anti-viral immunity and their numbers are reduced in patients with allergic asthma during RV-induced asthma exacerbations. This mechanism may be one explanation why RV-triggered clinical and pathologic outcomes are more severe in allergic patients than in healthy subjects. Funding ERC FP7 Advanced grant 233015, MRC Centre Grant G1000758, Asthma UK grant 08–048, NIHR Biomedical Research Centre funding scheme, NIHR BRC Centre grant P26095, the Predicta FP7 Collaborative Project grant 260895, RSF grant 19-15-00272, Megagrant No 14.W03.31.0024.
Issue Date: 1-Apr-2020
Date of Acceptance: 9-Mar-2020
URI: http://hdl.handle.net/10044/1/82823
DOI: 10.1016/j.ebiom.2020.102734
ISSN: 2352-3964
Publisher: Elsevier
Start Page: 1
End Page: 14
Journal / Book Title: EBioMedicine
Volume: 54
Copyright Statement: © 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
Medicine, Research & Experimental
General & Internal Medicine
Research & Experimental Medicine
Macrophage
Polarization
Rhinovirus
Asthma
Exacerbation
ACTIVATION-REGULATED CHEMOKINE
BRONCHIAL EPITHELIAL-CELLS
BRONCHOALVEOLAR LAVAGE
ALVEOLAR MACROPHAGES
MONONUCLEAR-CELLS
INDUCED SPUTUM
HUMAN BLOOD
GM-CSF
POLARIZATION
DEFICIENT
Asthma
Exacerbation
Macrophage
Polarization
Rhinovirus
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
Medicine, Research & Experimental
General & Internal Medicine
Research & Experimental Medicine
Macrophage
Polarization
Rhinovirus
Asthma
Exacerbation
ACTIVATION-REGULATED CHEMOKINE
BRONCHIAL EPITHELIAL-CELLS
BRONCHOALVEOLAR LAVAGE
ALVEOLAR MACROPHAGES
MONONUCLEAR-CELLS
INDUCED SPUTUM
HUMAN BLOOD
GM-CSF
POLARIZATION
DEFICIENT
1103 Clinical Sciences
1117 Public Health and Health Services
Publication Status: Published
Article Number: UNSP 102734
Online Publication Date: 2020-04-09
Appears in Collections:National Heart and Lung Institute



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