Inflammatory exacerbation and inadequate interferone response to RV1b infection in HDM-sensitized lung tissue

Millions of asthmatics suffer from virus induced exacerbation mainly caused by rhinovirus (RV). Insufficient virus elimination and inadequate immune response are assumed to be responsible for exacerbation. Therefore, in this study the impact of an asthmatic background on the anti-viral and pro-inflammatory immune response was investigated in precision-cut lung slices (PCLS) of HDM-sensitized mice. Balb/c mice were sensitized and challenged with HDM or saline i.n. for 28 days. Then PCLS were sliced and infected with RV1b (105 TCID50/mL) or UV-inactivated RV1b for 48 h. HDM sensitization resulted in a TH-2/TH-17 dominated allergic immune response with significantly higher secretion of IL-4, IL-5, IL-10, IL-17A and IP-10 which was maintained ex vivo. RV1b infection significantly upregulated anti-viral cytokines such as IFN-v (954±311 vs. 566±111 ng/mg protein) and IP-10 (61±17 vs. 40±6 pg/mg protein) in healthy vs. asthmatic tissue, respectively. Furthermore, RV1b exacerbated IL-6 (40±13 vs. 102±16 ng/mg protein) and IL-4 (823±201 vs. 1374±340 pg/mg protein) secretion in asthmatic tissue ex vivo in comparison to the corresponding UV-control but remained unchanged in healthy tissue. Rupintrivir treatment significantly reduced cytokine secretion of IFN-a, IP-10, IL-4, IL-6 and MCP-1 in asthmatic tissue but had only an impact on MCP-1 levels in healthy tissue. The in vivo established asthmatic disease background by HDM-challenge maintained in cell culture, leads to a significantly dysregulated immune response to virus infection ex vivo. Further studies are required to reveal pathways involved in the mechanisms of virus-induced exacerbation of asthma.