Interrogation of the Effects of Rhinovirus on Th2 Promoting Pathways in Allergic Asthma
Saturday, March 5, 2016: 3:00 PM
Room 502A (Convention Center)
Rachana Agrawal, Ph.D., , ,
Rationale: The cellular mechanisms involved in rhinovirus (RV) induced asthma exacerbations in allergic subjects remain unclear. Basophils and dendritic cells (DCs) are key players in promoting Th2-driven inflammation in allergic asthma. We recently reported increased IgE responsiveness in circulating basophils of allergic asthmatics following RV exposure. Thus, we aimed to explore how RV infection impacts Th2-associated pathways in basophils and DCs.

Methods: Allergic asthmatics (n=9) were challenged intranasally with human rhinovirus 16. Flow cytometry was employed to capture global changes and extensively immunophenotype circulating basophils, myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in fresh whole blood obtained pre-inoculation (day 0), and during acute (day 4) and convalescent (day 21) phases post-inoculation. The multi-dimensionsal data analysis software, viSNE, was used to generate cell clusters of similar phenotypes.

Results: During the acute phase, viSNE analysis revealed enhanced expression of activation markers on mDCs and pDCs including HLA-DR and CD86, in conjunction with unconventional markers on mDCs including CD63 and prostaglandin D2 receptor (CRTH2). Furthermore, expression of intracellular Syk increased both in mDCs and pDCs, with little change in FcεRIα. By contrast, basophils displayed increased expression of FcεRIα, Syk and CD63, and levels of FcεRIα and CD63 remained elevated at day 21. At baseline, asthmatics segregated into IL-4hi (n=6) and IL-4lo (n=3) subgroups based on the percentage of IL-4+ basophils, mDCs and pDCs. Paradoxically, IL-4lo asthmatics developed more severe respiratory symptoms than the IL-4higroup.

Conclusions: Collectively these findings highlight complex cellular changes induced by RV infection in allergic asthmatics that do not fit a simple Th2 amplification model.