Bouyssi Alexandra, Déméautis Tanguy, Trecourt Alexis, Delles Marie, Agostini Fany, Monneret Guillaume, Glehen Olivier, Wallon Martine, Persat Florence, Devouassoux Gilles, Bentaher Abderrazzak, Menotti Jean
UR3738 Centre pour l'lnnovation en Cancérologie de Lyon, Team Inflammation and Immunity of the Respiratory Epithelium, Claude Bernard University-Lyon 1, 69495 Pierre Bénite, France.
Department of Pathology, South Lyon Hospital, Hospices Civils de Lyon, 69495 Pierre Bénite, France.
J Fungi (Basel). 2023 Jun 17;9(6):682. doi: 10.3390/jof9060682.
The airway exposure to spores (AFsp) is associated with an inflammatory response, potentially leading to allergic and/or chronic pulmonary aspergillosis. The aim of our study is to better understand the host response, first in vitro, then in vivo, following the chronic exposure of mice to AFsp. We investigated the inflammatory response to AFsp in cell mono- and co-culture systems with murine macrophages and alveolar epithelial cells. The mice were subjected to two intranasal instillations using 10 AFsp. Their lungs were processed for inflammatory and histopathological analyses. In cell culture, the gene expressions significantly increased for TNF-α, CXCL-1, CXCL-2, IL-1β, IL-1α and GM-CSF in macrophages, with these increases being limited for TNF-α, CXCL-1 and IL-1α in epithelial cells. In co-culture, increases in the TNF-α, CXCL-2 and CXCL-1 gene expressions were observed to be associated with increased protein levels. The in vivo lung histological analyses of mice challenged by AFsp showed cellular infiltrates in the peribronchial and/or alveolar spaces. A Bio-Plex approach on the bronchoalveolar lavage revealed significant increases in the protein secretion of selected mediators of the challenged mice compared to the unchallenged mice. In conclusion, the exposure to AFsp resulted in a marked inflammatory response of macrophages and epithelial cells. These inflammatory findings were confirmed in mouse models associated with lung histologic changes.
气道暴露于孢子（AFsp）与炎症反应相关，可能导致变应性和/或慢性肺曲霉病。我们研究的目的是更好地了解小鼠长期暴露于AFsp后，首先在体外，然后在体内的宿主反应。我们在小鼠巨噬细胞和肺泡上皮细胞的细胞单培养和共培养系统中研究了对AFsp的炎症反应。给小鼠进行两次鼻内滴注10个AFsp。对它们的肺进行炎症和组织病理学分析。在细胞培养中，巨噬细胞中TNF-α、CXCL-1、CXCL-2、IL-1β、IL-1α和GM-CSF的基因表达显著增加，而上皮细胞中TNF-α、CXCL-1和IL-1α的增加有限。在共培养中，观察到TNF-α、CXCL-2和CXCL-1基因表达的增加与蛋白质水平的增加相关。对受AFsp攻击的小鼠进行的体内肺组织学分析显示，支气管周围和/或肺泡间隙有细胞浸润。支气管肺泡灌洗的生物芯片方法显示，与未受攻击的小鼠相比，受攻击小鼠的选定介质的蛋白质分泌显著增加。总之，暴露于AFsp导致巨噬细胞和上皮细胞出现明显的炎症反应。这些炎症发现在与肺组织学变化相关的小鼠模型中得到了证实。
