Hong Ji Eun, Kye Yoon-Chul, Park Sung-Moo, Cheon In Su, Chu Hyuk, Park Byung-Chul, Park Yeong-Min, Chang Jun, Cho Jae-Ho, Song Man Ki, Han Seung Hyun, Yun Cheol-Heui
Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, South Korea.
Center for Food and Bioconvergence, Seoul National University, Seoul, South Korea.
Front Microbiol. 2019 Mar 12;10:447. doi: 10.3389/fmicb.2019.00447. eCollection 2019.
Respiratory syncytial virus (RSV) is a major pathogen that infects lower respiratory tract and causes a common respiratory disease. Despite serious pathological consequences with this virus, effective treatments for controlling RSV infection remain unsolved, along with poor innate immune responses induced at the initial stage of RSV infection. Such a poor innate defense mechanism against RSV leads us to study the role of alveolar macrophage (AM) that is one of the primary innate immune cell types in the respiratory tract and may contribute to protective responses against RSV infection. As an effective strategy for enhancing anti-viral function of AM, this study suggests the intranasal administration of spore which induces expansion of AM in the lung with activation and enhanced production of inflammatory cytokines along with several genes associated with M1 macrophage differentiation. Such effect by spore on AM was largely dependent on TLR-MyD88 signaling and, most importantly, resulted in a profound reduction of viral titers and pathological lung injury upon RSV infection. Taken together, our results suggest a protective role of AM in RSV infection and its functional modulation by spore, which may be a useful and potential therapeutic approach against RSV.
呼吸道合胞病毒(RSV)是一种主要感染下呼吸道并引发常见呼吸道疾病的病原体。尽管该病毒会导致严重的病理后果,但控制RSV感染的有效治疗方法仍未解决,同时RSV感染初期诱导的固有免疫反应也很弱。这种针对RSV的固有防御机制薄弱促使我们研究肺泡巨噬细胞(AM)的作用,AM是呼吸道主要的固有免疫细胞类型之一,可能有助于对RSV感染产生保护性反应。作为增强AM抗病毒功能的有效策略,本研究表明鼻内给予孢子可诱导肺内AM扩增,激活并增强炎性细胞因子以及与M1巨噬细胞分化相关的多个基因的产生。孢子对AM的这种作用很大程度上依赖于TLR-MyD88信号传导,最重要的是,在RSV感染后可显著降低病毒滴度和肺部病理损伤。综上所述,我们的结果表明AM在RSV感染中具有保护作用,且孢子可对其进行功能调节,这可能是一种针对RSV的有用且潜在的治疗方法。