Intranasal exposure of poly (I:C) exacerbates OVA-induced allergic asthma by causing a major shift in the immune...

Viral respiratory infections are the major cause of exacerbation of allergic asthma, often resulting in increased emergency visits and hospitalizations. However, the understanding of the immune pathways at the cellular/molecular level under the conditions is lacking. Therefore, the present work was designed to elucidate the complex interplay of immune response under the settings mimicking exacerbation of allergic asthma upon viral infection using mouse model of the condition. Mice were sensitized & challenged with Ovalbumin (OVA) to induce allergic asthma, and subsequently subjected to intranasal administration of poly(I:C), a viral mimetic. Poly(I:C) administration at a dose of 200 μg in OVA sensitized & challenged mice resulted in shift of airway inflammation from eosinophils to neutrophils and was accompanied by enhanced airway hyper-responsiveness. Interestingly, down-regulation of Th2 cytokines (IL-4/IL-5/IL-13), and steep production of pro-inflammatory cytokines (TNF-α/IL-6/KC/MCP-1) upon poly(I:C) exposure in allergic mice indicates a switch of immune response from adaptive to innate type. Further, poly(I:C) exposure exaggerated the OVA induced oxidative stress along with over-activation of MAPK/NF-κB in lung tissue. Such changes were accompanied with Th17/Treg imbalance. Despite the proven efficacy of corticosteroids in controlling eosinophilic inflammation in OVA-induced allergic asthma, failure of dexamethasone, a steroid class of drug to mitigate neutrophil-driven inflammation upon poly(I:C) exposure in allergic mice, suggests that innate immune mediators may contribute considerably during viral infection mediated exacerbation of allergic asthma. Overall, our study highlights the complexity of the immune response during viral induced exacerbation of allergic asthma and may provide new insights to tackle such steroid insensitive conditions.