Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, The University of Melbourne, Melbourne, VIC, Australia.
Front Immunol. 2020 May 12;11:887. doi: 10.3389/fimmu.2020.00887. eCollection 2020.
Exosomes are extracellular vesicles secreted by cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighboring or distant cells. While a role for exosomes in antimicrobial defense has recently emerged, currently very little is known regarding the nature and functional relevance of exosomes generated , particularly during an active viral infection. Here, we characterized exosomes released into the airways during influenza virus infection. We show that these vesicles dynamically change in protein composition over the course of infection, increasing expression of host proteins with known anti-influenza activity, and viral proteins with the potential to trigger host immune responses. We show that exosomes released into the airways during influenza virus infection trigger pulmonary inflammation and carry viral antigen that can be utilized by antigen presenting cells to drive the induction of a cellular immune response. Moreover, we show that attachment factors for influenza virus, namely α2,3 and α2,6-linked sialic acids, are present on the surface of airway exosomes and these vesicles have the ability to neutralize influenza virus, thereby preventing the virus from binding and entering target cells. These data reveal a novel role for airway exosomes in the antiviral innate immune defense against influenza virus infection.
外泌体是由细胞分泌的细胞外囊泡，在细胞间通讯中具有重要的生物学功能，可将具有生物活性的蛋白质、脂质和 RNA 转移到邻近或远处的细胞。虽然外泌体在抗菌防御中的作用最近已经显现，但目前对于在活跃的病毒感染期间产生的外泌体的性质和功能相关性知之甚少。在这里，我们描述了流感病毒感染期间释放到气道中的外泌体。我们表明，这些囊泡在感染过程中其蛋白质组成会动态变化，增加了具有已知抗流感活性的宿主蛋白和具有潜在引发宿主免疫反应的病毒蛋白的表达。我们表明，流感病毒感染期间释放到气道中的外泌体可引发肺部炎症，并携带病毒抗原，这些抗原可被抗原呈递细胞利用来驱动细胞免疫反应的诱导。此外，我们表明，流感病毒的附着因子，即α2,3 和 α2,6 连接的唾液酸，存在于气道外泌体的表面，这些囊泡具有中和流感病毒的能力，从而防止病毒结合并进入靶细胞。这些数据揭示了气道外泌体在抗病毒固有免疫防御中针对流感病毒感染的新作用。
