Of the therapeutic options developed against viral infections, clinical grade recombinant type I IFNs, (IFN-α/β) or type III IFNs (IFN-λ) raised much hope and interest among researchers. IFN-λ is particularly relevant as a gatekeeper of mucosal immunity: as we recently reported, it is able to induce an antiviral state, and simultaneously limits inflammation-driven tissue damage (The Journal of Experimental Medicine, 2020). Although IFN-λ’s acute antiviral activity is well-recognized, if and how prolonged exposure to this IFN might change the physiology of the lung remained largely overlooked. We demonstrated that, in a mouse model that mimics prolonged viral infection, IFN-λ decreases the effectiveness of the lung barrier, and predisposes to a lethal secondary infection with the Gram-positive bacterium Staphylococcus aureus (Science, 2020). Our findings give a potent mandate for rethinking the pathophysiological role of IFN-λ, and for avoiding its use in the most severe COVID-19 cases, which often develop superinfections.

Currently, we are further investigating how IFN-λ modifies the immune response elicited in the lung during viral and bacterial infections. By using traditional immunological techniques and cutting-edge omics approaches -such as single cell RNAseq and single cell proteomics- we will unravel how acute and prolonged exposure to microbial stimuli shapes the cellular and molecular landscape of the lung.

ZanoniLab

Histology of the lung of a mouse. Credit to Dr. Broggi