Interleukin-1 receptor-associated kinase M (IRAK-M) promotes human rhinovirus infection in lung epithelial cells via the autophagic pathway.
Human rhinovirus (HRV) is the most common viral etiology in acute exacerbations of asthma. However, the exact mechanisms underlying HRV infection in allergic airways are poorly understood. IL-13 increases interleukin-1 receptor associated kinase M (IRAK-M) and subsequently inhibits airway innate immunity against bacteria. However, the role of IRAK-M in lung HRV infection remains unclear. Here, we provide the first evidence that IRAK-M over-expression promotes lung epithelial HRV-16 replication and autophagy, but inhibits HRV-16-induced IFN-β and IFN-λ1 expression. Inhibiting autophagy reduces HRV-16 replication. Exogenous IFN-β and IFN-λ1 inhibit autophagy and HRV-16 replication. Our data indicate the enhancing effect of IRAK-M on epithelial HRV-16 infection, which is partly through the autophagic pathway. Impaired anti-viral interferon production may serve as a direct or an indirect (e.g., autophagy) mechanism of enhanced HRV-16 infection by IRAK-M over-expression. Targeting autophagic pathway or administrating anti-viral interferons may prevent or attenuate viral (e.g., HRV-16) infections in allergic airways.
Department of Medicine, National Jewish Health, Denver, CO, USA.
Qun
Q
Wu
Linda F
LF
van Dyk
Di
D
Jiang
Azzeddine
A
Dakhama
Liwu
L
Li
Steven R
SR
White
Ashley
A
Gross
Hong Wei
HW
Chu
D001343:Autophagy; D004847:Epithelial Cells / Q000821:virology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D016899:Interferon-beta / Q000037:antagonists & inhibitors; D007372:Interferons; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism*; D007378:Interleukins / Q000037:antagonists & inhibitors; D012229:Rhinovirus / Q000502:physiology*; D014779:Virus Replication; D000095022:Interferon Lambda
D016899:Interferon-beta; D007372:Interferons; D053592:Interleukin-1 Receptor-Associated Kinases; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C507771:IRAK3 protein, human
ALI culture; Air-liquid interface culture; Airway epithelial cells; Autophagy; HRV; Human rhinovirus; IFN-β; IFN-λ1; IRAK-M; Interferon-β; Interferon-λ1; Interleukin-1 receptor associated kinase M; PE; Viral replication; phosphatidylethanolamine