Peripheral Blood Mononuclear Cells from Patients with Bronchial Asthma Show Impaired Innate Immune Responses to Rhinovirus in vitro

Abstract

Background: Asthmatic patients have a higher susceptibility to rhinovirus (RV) infection, and impaired IFN-β and IFN-λ production has been demonstrated in bronchial epithelial cells from asthmatic adults upon exposure to RV. However, the mechanisms underlying the increased susceptibility of asthmatic patients to RV infection remain poorly understood. The present study aimed to elucidate the characteristics of the immune responses of asthmatic patients’ peripheral blood mononuclear cells (PBMCs) to RV exposure. Methods: PBMCs obtained from 3 different age groups (2–6 years: young-children group; 7–19 years: youth group; ≧20 years: adult group) of asthmatic patients and nonasthmatic control subjects were stimulated with RV-14 for 72 h. Healthy adults with a history of childhood asthma were also enrolled. The concentrations of IFN-α, IL-6, TNF-α, IL-10, and soluble Fas ligand (sFasL) in the culture supernatants were measured by ELISA. Results: When compared with age-matched control subjects, IFN-α production was significantly lower in the asthmatic youth group. IL-6, TNF-α, IL-10, and sFasL productions were significantly lower in both the asthmatic youth group and the adult group. Such impaired responses were not found in healthy adults with a history of childhood asthma. No significantly different responses were found between the asthmatics and controls in the young-children group, whereas young asthmatic children with persistent wheeze during a 2-year follow-up showed significantly lower IL-10 production than those without wheeze. Conclusions: These results imply the involvement of impaired production of both IFN-α and inflammatory cytokines seen in asthmatic patients’ PBMCs upon exposure to RV in the higher susceptibility of those patients to RV infection.

Rhinovirus 16–induced IFN-α and IFN-β are deficient in bronchoalveolar lavage cells in asthmatic patients

“…31 It is possible that defective rhinovirus-induced interferon induction is in part specific to the lung environment; however, demonstration of defective interferon induction with rhinovirus and other viruses in nonlung cells in asthmatic patients makes this less likely. [7][8][9]22 In this study BAL cells and PBMCs were stimulated with the same dose of RV16 but behaved differently in response to stimulation, with a more robust IFN-a and IFN-a2 response observed in PBMCs compared with that seen in BAL cells. If defective type I interferon induction is only apparent at more subtle levels of viral stimulation, this might explain the failure to observe defective interferon induction in PBMCs in this study.…”

“…PBMCs from atopic asthmatic children have also demonstrated defective IFN-a induction after RV14 infection. 7 PBMCs contain cells other than monocytes, including plasmacytoid dendritic cells, which make up less than 1% of mononuclear cells but produce the majority of IFN-a. 31 It is possible that defective rhinovirus-induced interferon induction is in part specific to the lung environment; however, demonstration of defective interferon induction with rhinovirus and other viruses in nonlung cells in asthmatic patients makes this less likely.…”

“…[7][8][9]22 IFN-a and IFN-b protein levels were also measured in PBMC cell supernatants 8, 24, and 48 hours after RV16 stimulation to investigate whether defective RV16-induced type I interferon also occurred in PBMCs from adults. Because deficient virus (respiratory syncytial virus, Newcastle disease virus, or both)-induced IFN-a2 protein in PBMCs from asthmatic adults and children has been reported, 8,9 levels of IFN-a2 protein were also assessed.…”

“…Defective rhinovirus-induced interferon in asthmatic patients has been reported for 2 types of interferons in 3 different cell types: IFN-b in primary human bronchial epithelial cells (HBECs), IFN-a in PBMCs from children, and IFN-l in HBECs and bronchoalveolar lavage (BAL) cells. 3,4,6,7 Deficiency has been associated with viral load in vitro 4 and viral load and markers of exacerbation severity in vivo. 3 Deficient IFN-a subtype 2 (IFN-a2) response to respiratory syncytial virus and Newcastle disease virus has been reported in PBMCs from atopic asthmatic adults and children.…”

Toll-like Receptor 7 Is Reduced in Severe Asthma and Linked to an Altered MicroRNA Profile

“…This vulnerability is believed to be caused by an impaired IFN response to virus (7)(8)(9)(10). IFN is an antiviral cytokine, and its production is triggered when pattern recognition receptors (PRRs) are activated by viral genomic material (11).…”