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

Abstract

Background: Macrophages (ML) can be M1/M2 polarized by Th1/2 signals, respectively. M2-like ML 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 ML phenotype responses to rhinovirus (RV) infection in vitro and (ii) to assess ML 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 ML (MDM, from 3À6 independent donors) in vitro and evaluated frequencies of M1/M2-like bronchoalveolar lavage (BAL) ML 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 ML in asthma during experimental RV16 infection compared to baseline (P = 0.024). Interpretation: Human M1-like BAL ML 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.

Exosomes from human umbilical cord mesenchymal stem cells attenuate the inflammation of severe steroid-resistant asthma by reshaping macrophage polarization

“…Macrophages are the most abundant immune cells in lung tissue (approximately 70% of all immune cells) and play central roles in regulating airway inflammation and airway remodeling [ 6 , 7 ]. Macrophages are categorized into classic activated (M1) and alternative activated (M2) phenotypes based on the expression of specific cytokines and surface markers [ 8 ]. During the acute exacerbation of SSRA, M1 macrophages have been shown to secrete large amounts of inflammatory mediators (include TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS)) [ 9 ].…”

Viruses and asthma: the role of common respiratory viruses in asthma and its potential meaning for SARS‐CoV‐2

“…The reduced antiviral function of eosinophils in asthmatic patients during respiratory viral infections could contribute to virus‐induced asthma exacerbations 12 . In line with this observation, it has been shown that the frequency of M1‐like macrophages, which are involved in antiviral responses through type I and III interferon production, were decreased in asthmatic patients during asthma exacerbation induced by RV 94 . These results seem to indicate that several immune cells that normally have an antiviral function in healthy individuals are found in lower frequency in asthmatic patients or with an altered functionality, thus promoting respiratory viral infection with detrimental consequences for asthmatic symptoms.…”

Sex differences in innate anti-viral immune responses to respiratory viruses

“…IFN-γ is the only type II IFN, and it also is very important in promoting innate immune responses principally by activating natural killer (NK) cells which are important in innate immune defense against virus infections, by rapid killing of virus-infected cells(21). IFN-γ also primes other immune cells such as macrophages, to release anti-viral cytokines(22) and to phagocytose infected cells(21). IFN-γ has been shown to suppress mouse coronavirus replication, though this was dependent, in part, on induction of type I IFN secretion(23).…”