Increased Nasal Plasmacytoid Dendritic Cells Are Associated with Recurrent Wheezing Following Severe RSV Bronchiolitis

Kitcharoensakkul, Maleewan

Rationale: Dendritic cells (DCs) play an important role in anti-viral responses and regulating differentiation of T cells. We hypothesized immune dysregulation of DC may contribute to recurrent wheezing in susceptible children following severe RSV bronchiolitis.

Methods: From 2009 – 2013, we prospectively enrolled infants < 1 year of age hospitalized with their first episode of RSV-confirmed bronchiolitis into the RSV Bronchiolitis in Early Life 2 (RBEL-2) cohort. Nasal wash mononuclear cells were labeled for plasmacytoid DCs (pDCs): Lin^-(CD3, CD19, CD14, CD20, CD16, CD56)_,CD123⁺, HLA-DR⁺ and myeloid DCs (mDCs): Lin^- CD11c⁺ HLA-DR⁺cells. Blood DC were isolated using Blood Dendritic Cell Enumeration Kit and labeled for pDCs, mDC1, and mDC2 by labeling with anti-BDCA-2, anti-BDCA1, and anti-BDCA-3 antibodies respectively.

Results: 181 participant’s (58% male, 47% Caucasian) mean age of entry was 4.3±3.0 months. After 38±19 months follow-up, 75 (41.4%) had recurrent wheezing (3 or more wheezing episodes) and 50 (27.6%) had no wheezing. The recurrent wheezing group had higher proportion of upper airway pDCs, compared to no wheezing (1.72 ± 2.22 vs. 0.78 ± 1.65%, p = 0.04, adjusted p= 0.016) and were more likely to be African-American OR 6.1 (95%CI 1.7-26.0) in a multivariate model. There were no differences in nasal mDC and blood DCs between these groups.

Conclusions: Children with recurrent wheezing following severe RSV bronchiolitis had higher proportion of nasal pDCs which may reflect a heightened antiviral response in the airway leading to the subsequent development of asthma.