Mitigation of influenza-mediated inflammation by immunomodulatory matrix-bound nanovesicles

Cytokine storm describes a life-threatening, systemic inflammatory syndrome characterized by elevated levels of proinflammatory cytokines and immune cell hyperactivation associated with multi-organ dysfunction. Matrix-bound nanovesicles (MBV) are a subclass of extracellular vesicle shown to down-regulate proinflamma-tory immune responses. The objective of this study was to assess the efficacy of MBV in mediating influenza -induced acute respiratory distress syndrome and cytokine storm in a murine model. Intravenous administration of MBV decreased influenza-mediated total lung inflammatory cell density, proinflammatory macrophage fre-quencies, and proinflammatory cytokines at 7 and 21 days following viral inoculation. MBV decreased long-lasting alveolitis and the proportion of lung undergoing inflammatory tissue repair at day 21. MBV increased the proportion of activated anti-viral CD4+ and CD8+ T cells at day 7 and memory-like CD62L+ CD44+, CD4+, and CD8+ T cells at day 21. These results show immunomodulatory properties of MBV that may benefit the treatment of viral-mediated pulmonary inflammation with applicability to other viral diseases such as SARS-CoV-2.

Automated summary

Cytokine storm is a life-threatening inflammatory syndrome characterized by elevated proinflammatory cytokines and immune cell hyperactivation. Matrix-bound nanovesicles (MBV) have been shown to down-regulate proinflammatory immune responses. This study assessed the efficacy of MBV in a murine model of influenza-induced acute respiratory distress syndrome and cytokine storm. Intravenous administration of MBV decreased total lung inflammatory cell density, proinflammatory macrophages, and cytokines following viral inoculation, while also increasing the proportion of activated anti-viral T cells. These findings suggest that MBV has immunomodulatory properties that may be beneficial in treating viral-mediated pulmonary inflammation, including diseases such as SARS-CoV-2.