Fig. 2

Effects of RV infection on airway smooth muscle and fibroblasts. Exposure of RV on airway epithelium results in downstream responses that augment migration, proliferation, and cellular function of sub-epithelial structural cell types. (1) Infected airway epithelial cells (AEC) produce FGF2, CXCL8, IP-10, and alarmins such as IL-33 and TSLP that act on airway fibroblasts and airway smooth muscle (ASM) to induce sub-epithelial thickening, cell proliferation, and mobilization surrounding the airway. Smooth muscle may also produce IL-33 that contributes to remodeling-associated cytokines induced by RV infection. (2) Fibroblasts accumulation with RV infection occurs in response to FGF2 and CXCL8 along with (3) smooth muscle migration through the sub-epithelial layer. (4) RV infection may promote fibroblast-to-myofibroblast transition (FMT), resulting in increased myofibroblast numbers surrounding the airway. (5) Extracellular matrix deposition by smooth muscle and fibroblasts, as well as MMP activity, is upregulated during RV infection. (6) RV infection of the airway induces smooth muscle hyperplasia and hypertrophy. (7) Altogether, airway RV exposure promotes airway hyperresponsiveness (AHR) in a multifactorial manner mediated by both sub-epithelial thickening and augmentation of contraction and relaxation responses in airway smooth muscle. Created with BioRender.com