Paper Details
- Masashi Tachibana (Project for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University / Global Center for Medical Engineering and Informatics, Osaka University / Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University / tacci@phs.osaka-u.ac.jp)
1) Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang, School of Medicine, Hangzhou City University, China , 2) Project for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University , 3) Laboratory of Nano-design for Innovative Drug Development, Graduate School of Pharmaceutical Sciences, Osaka University , 4) Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, Osaka University , 5) Vaccine Creation Group, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University , 6) Research Center for Genome & Medical Sciences, Tokyo Metropolitan Institute of Medical Science , 7) BIKEN Center for Innovative Vaccine Research and Development, The Research Foundation for Microbial Diseases of Osaka University , 8) Global Center for Medical Engineering and Informatics, Osaka University , 9) Center for Advanced Modalities and DDS, Osaka University , 10) Center for Infectious Disease Education and Research, Osaka University , 11) Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University
In humans, influenza A virus (IAV) causes mild to severe respiratory disease, posing a major threat to public health worldwide. Increasing evidence suggests that myeloid-derived suppressor cells (MDSCs) are involved in viral infection outcomes in genetically modified mice; however, the mechanisms by which MDSCs contribute to lung pathology under normal genetic conditions remain controversial. In the present study, we intranasally infected mice with mouse-adapted IAV (A/Puerto Rico/8/1934 [PR8]) and adoptively transferred MDSCs differentiated in vitro intravenously to assess their functional relevance in vivo. After PR8 infection, the adoptive transfer of MDSCs significantly improved the survival of mice. Furthermore, MDSC transfer increased CD4+ T cell and eosinophil infiltration into the lungs and decreased interleukin-6 and tumor necrosis factor-α levels in the bronchoalveolar lavage fluid. However, the viral load did not significantly decrease; this suggests that MDSCs affect virus clearance. Inducible nitric oxide synthase (iNOS) is a key factor responsible for the immunosuppressive activity of MDSCs. However, the transfer of Nos2-deficient MDSCs can decrease PR8 infection-induced mortality; nevertheless, the absence of iNOS in MDSCs did not affect the infiltration of inflammatory cells into the lung, suggesting that MDSCs function independently of their iNOS expression and downstream pathways. Taken together, our findings suggest that transferred MDSCs decrease IAV disease-induced mortality in vivo in an iNOS-independent manner. The adoptive cellular transfer of MDSCs may be an attractive therapeutic strategy for IAV infections.
