Role for CD11c expressing cells in generation of pulmonary vascular leak during a respiratory viral infection
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Jennifer L Santoro, Michelle Rohlfing, Syed-Rehan A Hussain, PhD, Mitchell H. Grayson, MD FAAAAI
RATIONALE: Sendai virus (SeV) infection in mice drives development of post-viral atopic disease through a mechanism that requires IgE and expression of FcεRI on lung CD11c+ dendritic cells (DC). A significant component of the antiviral immune response is development of pulmonary vascular leak, which we have demonstrated to be IgE and FcεRI dependent. This study was undertaken to determine if DC FcεRI was required to generate vascular leak during a respiratory viral infection.

METHODS: C57BL6 (WT) or FceRIa–/– mice were inoculated with SeV. One day before inoculation with SeV, FceRIa–/– mice intranasally received 3x105 CD11c+ cells, which were isolated from lungs of naïve WT or FceRIa–/– mice by positive immunomagnetic selection. On day 8 PI, Evans Blue Dye (EBD; binds albumin to quantify vascular leak) was given intravenously, and 1 hour later pulmonary vasculature flushed with PBS, and EBD concentration in lung homogenates determined by spectrophotometry.

RESULTS: As measured by fold EBD, FceRIa–/– mice failed to develop vascular leak compared to WT mice (1.52+/-0.34 versus 3.24+/-0.17, mean±SEM fold EBD concentration, FceRIa–/– versus WT mice, p=0.0047, n=4-6). Transfer of WT but not FceRIa–/– DC restored vascular leak to FceRIa–/– mice (2.48+/-0.22 versus 1.50+/-0.15, mean±SEM µg/mL EBD, WT DC versus FceRIa–/– DC, p=0.0055, n=6-8).

CONCLUSIONS: The development of pulmonary vascular leak during an antiviral immune response depends upon FcεRI expressing DC. The IgE dependent mechanism through which DC induce vascular leak in this model is not known, but is an area of active study.