Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection

Habibi MS, Thwaites RS, Chang M, Jozwik A, Paras A, Kirsebom F, Varese A, Owen A, Cuthbertson L, James P, Tunstall T, Nickle D, Hansel TT, Moffatt MF, Johansson C, Chiu C, Openshaw PJM

​Why does RSV exposure in one individual lead to disease, while another individual does not experience symptoms at all? Besides, how can a virus reinfect individuals that already have a specific viral immune response available? In this Science paper, Habibi and his colleagues present mucosal neutrophil activation as a new factor involved in RSV susceptibility and protection. They studied the nasal mucosa by transcriptional and proteomic analyses in 58 healthy volunteers right before RSV inoculation and during the following days of infection. An active neutrophilic inflammatory status in the airways at the time of viral exposure was found to predispose to symptomatic infection. This effect might be mediated by a reduction in antiviral inflammatory responses directly after viral exposure. In addition, an early immune response to the infection with enriched IL-17 signaling and corresponding pathways was associated with protection from RSV-related symptoms. Further experiments in mice showed that chemokine induced neutrophil recruitment to the airway before viral exposure enhances disease severity and leads to an elevated cytotoxic CD8+ T cell response. These findings shed light on mechanisms of viral susceptibility and suggest new targets for RSV intervention. Furthermore, neutrophilic inflammation of the airways might not only be important in RSV infection, but in other viral respiratory diseases as well, such as in the SARS-CoV-2 infection. 
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Download paper of the month | October 2020