Association of the Infant Gastrointestinal Microbiome with Nocturnal Symptoms in Children with Asthma

Abstract

E S D A Y 887 Human Rhinovirus Species Induce Differential Antiviral and Inflammatory Responses in Peripheral Blood Mononuclear Cells Alalia W. Berry, MD, Megan Yanny, Mark DeVries, Yury Bochkov, PhD, Victoria Rajamanickam, James E. Gern, MD FAAAAI, Robert F. Lemanske, Jr, MD, FAAAAI, Daniel J. Jackson, MD; University of Wisconsin School of Medicine and Public Health, University of Wisconsin, University of Wisconsin School of Medicine and Public Health, Madison, WI, University of Wisconsin Hospitals and Clinics, Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI. RATIONALE: Human rhinoviruses (RV) are a common cause of asthma exacerbations in children. RV-C causes more severe respiratory illnesses than RV-A or RV-B. However, the mechanism(s) underlying this observation remain unclear. Prior studies have shown that children with allergic asthma have impaired antiviral responses in peripheral blood mononuclear cells (PBMCs). We hypothesize that RV-C would induce differential antiviral responses in PBMCs when compared to RV-A and RV-B. METHODS: PBMCs were isolated from peripheral blood samples of 40 children ages 13-14 years enrolled in the Childhood Origins of ASThma (COAST study). PBMCs were incubated with RV-A36, RV-B52, RV-C15 or medium alone for 22 hours. Supernatants were frozen at -80 and interferons (IFN-alpha2, IFN-gamma, IFN-lambda1) were measured using multiplex ELISA. Interferon levels induced by the different RV species were compared. RESULTS: Stimulation with RV-A led to significantly greater production of IFN-alpha2 and IFN-lambda1 compared to RV-B, RV-C, or control [(median IFN-alpha2: RV-A 1000 pg/ml, RV-B 4 pg/ml, RV-C <3.2 pg/ml, control <3.2 pg/ml), p<0.0001; (median IFN-lambda1: RV-A 142 pg/ml, RV-B <12.2 pg/ml, RV-C <12.2 pg/ml, control <12.2 pg/ml, p<0.0001]. All RV species increased production of IFN-gamma compared to control, with RV-C leading to the least IFN-gamma [(median IFN-gamma: RV-A 55 pg/ml, RV-B 15 pg/ml, RV-C 6 pg/ml, control <3.2 pg/ml), p<0.0001)]. CONCLUSIONS: PBMCs stimulated with RV-C15 secreted significantly less interferon compared to cells stimulated with other RV species. RV-C may evade the antiviral response of mononuclear cells in the airway, which could contribute to greater illness severity.