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

Background: Macrophages (M Phi) can be M1/M2 polarized by Th1/2 signals, respectively. M2-like M Phi 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 M Phi phenotype responses to rhinovirus (RV) infection in vitro and (ii) to assess M Phi 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 M Phi (MDM, from 3-6 independent donors) in vitro and evaluated frequencies of M1/M2-like bronchoalveolar lavage (BAL) M Phi 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(+)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 M Phi in asthma during experimental RV16 infection compared to baseline (P = 0.024). Interpretation: Human M1-like BAL M Phi 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. (C) The Authors. Published by Elsevier B.V.