Probiotics protect against RSV infection by modulating the microbiota-alveolar-macrophage axis

Abstract

Respiratory syncytial virus (RSV) is leading cause of respiratory tract infections in early childhood. Gut microbiota is closely related with the pulmonary antiviral immunity. Recent evidence shows that gut dysbiosis is involved in the pathogenesis of RSV infection. Therefore; pharmacological and therapeutic strategies aiming to readjust the gut dysbiosis are increasingly important for the treatment of RSV infection. In this study, we evaluated the therapeutic effects of a probiotic mixture on RSV-infected mice. This probiotic mixture consisted of Lactobacillus rhamnosus GG, Escherichia coli Nissle 1917 and VSL#3 was orally administered to neonatal mice on a daily basis either for 1 week in advance or for 3 days starting from the day of RSV infection. We showed that administration of the probiotics protected against RSV-induced lung pathology by suppressing RSV infection and exerting an antiviral response via alveolar macrophage (AM)-derived IFN-β. Furthermore, administration of the probiotics reversed gut dysbiosis and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria in RSV-infected mice, which consequently led to elevated serum SCFA levels. Moreover, administration of the probiotics restored lung microbiota in RSV-infected mice. We demonstrated that the increased production of IFN-β in AMs was attributed to the increased acetate in circulation and the levels of Corynebacterium and Lactobacillus in lungs. In conclusion, we reveal that probiotics protect against RSV infection in neonatal mice through a microbiota-AM axis, suggesting that the probiotics may be a promising candidate to prevent and treat RSV infection, and deserve more research and development in future.

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Fig. 1: Probiotics showed an antiviral response to RSV infection.
Fig. 2: Probiotics reversed gut dysbiosis.
Fig. 3: Probiotics increased the levels of SCFAs.
Fig. 4: Probiotics restored RSV-induced lung microbiota alteration.
Fig. 5: Probiotics may potentially activate the antiviral responses of alveolar macrophages.
Fig. 6: Probiotic pretreatment promoted IFN-β production in AMs.
Fig. 7: The antiviral effects of probiotic pretreatment are mediated through acetate.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81673412, 013038007001), Key R & D and promotion project of Henan Province (Science and technology tackling, Project No: 192102310431), the Jiangsu Key R&D Plan (Social Development) BE2019618, Six Talent Peaks in Jiangsu Province (YY-013), the Jiangsu Province TCM Science and Technology Development Plan Project (ZD201901), the Grant for Special Professors of Jiangsu (2015), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and The Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine Supported by the Subject of Academic priority discipline of Jiangsu Higher Education Institutions (ZYX03KF053).

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ZGL and GMP conceived and designed the experiments. JJJ, QMS, DYN, QW, HZ, FFQ, QSW and SFL performed the experiments. ZGL and QMS analyzed the data. JJJ wrote the manuscript.

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Correspondence to Guo-ming Pang or Zhi-gang Lu.

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The authors declare no competing interests.

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Ji, Jj., Sun, Qm., Nie, Dy. et al. Probiotics protect against RSV infection by modulating the microbiota-alveolar-macrophage axis. Acta Pharmacol Sin (2021). https://doi.org/10.1038/s41401-020-00573-5

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Keywords

  • respiratory syncytial virus
  • probiotics
  • gut microbiota
  • lung microbiota
  • alveolar macrophages
  • SCFAs

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