From bench to bedside: DNase in Rhinovirus-induced allergic asthma exacerbation
The most frequent cause of exacerbation in a patient with asthma is the viral respiratory infection. An interesting joint work between Imperial College London and the University of Liege in Belgium published in Nature Medicine suggests new therapeutic targets and the potential use of DNAse in Rhinovirus respiratory infection.
During viral infections in the airways there is an increase in neutrophils that with a process known as NETosis release NETs (neutrophil extracellular traps) in the extracellular space. NETs contain host dsDNA, neutrophil elastase, myeloperoxidase and other antimicrobial substances. The results of this study report that in a subject with asthma Rhinovirus infection induces neutrophils to release large amounts of host dsDNA in the upper airways and that this huge amount of DNA translates into a strong Th2 response and to the severity of the exacerbation. The amount of NETs and host dsDNA in the upper airways correlates positively with the levels of IL-5 and IL-13 both in the upper and lower airways. Once that these events were reproduced in the mice model, the effect of DNase on Th2 response was assessed. The reduction of host dsDNA in the extracellular space of the upper airways induced by DNAse was associated with the reduction of eosinophilic lung inflammation, mucus production, airway hyperresponsiveness and serum IgE with an overall reduction of the Th2 response. These are still preliminary results and performed in mice but the neutrophil process NETosis could become a target to limit the severity of viral exacerbations and DNase might have a role also in the patient with asthma.
Toussaint M, Jackson DJ, Swieboda D, Guedán A, Tsourouktsoglou TD, Ching YM, Radermecker C, Makrinioti H, Aniscenko J, Edwards MR, Solari R, Farnir F, Papayannopoulos V, Bureau F, Marichal T, Johnston SL. Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation. Nat Med. 2017 Jun;23(6):681-691