Jason P Lynch, Rhiannon B Werder, Zhixuan Loh, Md Al Amin Sikder, Bodie Curren, Vivian Zhang, Matthew J Rogers, Katie Lane, Jennifer Simpson, Stuart B Mazzone, Kirsten Spann, John Hayball, Kerrilyn Diener, Mark L Everard, Christopher C Blyth, Christian Forstner, Paul G Dennis, Nida Murtaza, Mark Morrison, Páraic Ó Cuív, Ping Zhang, Ashraful Haque, Geoffrey R Hill, Peter D Sly, John W Upham, Simon Phipps
Respiratory syncytial virus-bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after reinfection. pDC depletion ablated interferon production and increased viral load; however, the heightened immunopathology and susceptibility to subsequent asthma stemmed from a failure to expand functional neuropilin-1+ regulatory T (T reg) cells in the absence of pDC-derived semaphorin 4a (Sema4a)...
February 5, 2018: Journal of Experimental Medicine