Probiotics Confers Protection Against RSV Infections by Regulating Gut and Lung Microbiotas to Activate Antiviral Responses of Alveolar Macrophage

Abstract

Background: Respiratory syncytial virus(RSV) is leading cause of respiratory tract infections in early childhood. The gut microbiotas are critical in shaping the pulmonary antiviral immunity. Hence, the endeavors to defense against RSV infection by manipulating gut microbiotas are currently undergoing. Methods: The mice were infected intranasally with RSV to establish RSV infected mice model, and model mice were intragastrically administered probiotics for evaluating therapeutic effect in vivo. Multiple molecular experiments including real-time PCR, Western blot, flow cytometry and immunofluorescence were used to elucidate the underlying mechanisms. The gut and lung microbiota composition was profiled through 16S rRNA sequencing. Concentration of short-chain fatty acid (SCFA) was examined using GC-MS. Findings: Our results showed probiotics markedly reduced lung RSV replication and improved lung pathology. Further experimental data present probiotics modified gut microbiotas composition and altered the metabolic profiles in RSV infected mice. In particular, this agent significantly elevated the levels of gut microbiotas producing short chain fat acid(SCFA), which was evidenced up-regulated the IFNβ production. Moreover, probiotics also resumed the lung microbiotas in RSV infected mice. Specially, probiotics increased the abundance of Corynebacterium and Lactobacillus in lung via the up-regulated SCFAs, consequently, leading to induction of IFNβ production in alveolar macrophages. Interpretation: These results demonstrated the effectiveness of probiotics in treating RSV infections and its involved mechanisms are through regulating the gut and lung microbiotas to activate antiviral responses of alveolar macrophage. Funding Statement: This work was supported by National Natural Science Foundation of China (81673412), the Natural Science Foundation of Jiangsu Province (BK20180825). Declaration of Interests: The authors declare no commercial or financial conflicts of interest. Ethics Approval Statement: All experimental procedures were performed in accordance with the National Institutes of Health Guidelines for Laboratory Animals and approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine(Permission Number: ACU-29(20161230)).