Abstract
Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and to unrelated immune triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflammation. However, helminthic immunomodulators have so far not been tested in virus-induced disease. We now report that AvCystatin prevents Th2-based immunopathology in vaccine-enhanced RSV lung inflammation, a murine model for bronchiolitis. AvCystatin ablated eosinophil influx, reducing both weight loss and neutrophil recruitment without impairing anti-viral immune responses. AvCystatin also protected mice from excessive inflammation following primary RSV infection, significantly reducing neutrophil influx and cytokine production in the airways. Interestingly, we found that AvCystatin induced an influx of CD4+ FoxP3+ interleukin-10-producing T cells in the airway and lungs, correlating with immunoprotection, and the corresponding cells could also be induced by adoptive transfer of AvCystatin-primed F4/80+ macrophages. Thus, AvCystatin ameliorates enhanced RSV pathology without increasing susceptibility to, or persistence of, viral infection and warrants further investigation as a possible therapy for virus-induced airway disease.
Highlights
Respiratory Syncytial virus (RSV) is the commonest single cause of hospitalization during infancy, resulting in approximately 160,000 deaths annually worldwide [1]
To test the ability of AvCystatin to modify virus-enhanced immunopathology we investigated its effects in primary RSV infection and two models of virus-induced lung eosinophilia in mice: RSV challenge of mice sensitised with recombinant vaccinia encoding the major surface glycoprotein G [23] and RSV challenge of formalin-RSV vaccinated mice (FI-RSV/ RSV) [24]
Testing the therapeutic potential of AvCystatin in viral lung disease, we show that it has beneficial effects in both primary and in vaccine-enhanced lung pathology
Summary
Respiratory Syncytial virus (RSV) is the commonest single cause of hospitalization during infancy, resulting in approximately 160,000 deaths annually worldwide [1]. The stated conflicts of interest do not alter our adherence to PLOS ONE policies on sharing data and materials. Bronchiolitis may be associated with recurrent wheezing and asthma in later life [3,4]. Vaccination with alum-adjuvanted formalininactivated RSV vaccine caused increased disease severity and deaths, probably associated with eosinophilic disease [5,6]. Prophylactic administration of the humanised anti-RSV monoclonal palivizumab (Synagis1) prevents infection in high-risk infants [7] and reduces the frequency of subsequent wheezing [8], but is costly. The great burden of RSV disease and the lack of an effective treatment underscores the importance of developing new intervention strategies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
