Rojas Diego A, Ponce Carolina A, Bustos Adriel, Cortés Vicente, Olivares Daniela, Vargas Sergio L
Instituto de Ciencias Biomédicas (ICB), Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8910132, Chile.
Programa de Microbiología y Micología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380492, Chile.
J Fungi (Basel). 2023 Apr 7;9(4):452. doi: 10.3390/jof9040452.
Inflammation and mucus hypersecretion are frequent pathology features of chronic respiratory diseases such as asthma and COPD. Selected bacteria, viruses and fungi may synergize as co-factors in aggravating disease by activating pathways that are able to induce airway pathology. infection induces inflammation and mucus hypersecretion in immune competent and compromised humans and animals. This fungus is a frequent colonizer in patients with COPD. Therefore, it becomes essential to identify whether it has a role in aggravating COPD severity. This work used an elastase-induced COPD model to evaluate the role of in the exacerbation of pathology, including COPD-like lung lesions, inflammation and mucus hypersecretion. Animals infected with developed increased histology features of COPD, inflammatory cuffs around airways and lung vasculature plus mucus hypersecretion. induced a synergic increment in levels of inflammation markers (Cxcl2, IL6, IL8 and IL10) and mucins (Muc5ac/Muc5b). Levels of STAT6-dependent transcription factors Gata3, FoxA3 and Spdef were also synergically increased in infected animals and elastase-induced COPD, while the levels of the mucous cell-hyperplasia transcription factor FoxA2 were decreased compared to the other groups. Results document that is a co-factor for disease severity in this elastase-induced-COPD model and highlight the relevance of STAT6 pathway in pathogenesis.
炎症和黏液高分泌是哮喘和慢性阻塞性肺疾病（COPD）等慢性呼吸道疾病常见的病理特征。特定的细菌、病毒和真菌可能作为辅助因子协同作用，通过激活能够诱导气道病理改变的途径来加重疾病。感染会在免疫功能正常和受损的人类及动物中引发炎症和黏液高分泌。这种真菌是COPD患者中常见的定植菌。因此，确定它是否在加重COPD严重程度中起作用变得至关重要。这项研究使用弹性蛋白酶诱导的COPD模型来评估其在病理加重过程中的作用，包括类似COPD的肺部病变、炎症和黏液高分泌。感染的动物出现了COPD组织学特征增加、气道和肺血管周围的炎症袖套以及黏液高分泌。诱导炎症标志物（Cxcl2、IL6、IL8和IL10）和黏蛋白（Muc5ac/Muc5b）水平协同增加。在感染的动物和弹性蛋白酶诱导的COPD中，STAT6依赖性转录因子Gata3、FoxA3和Spdef的水平也协同增加，而与其他组相比，黏液细胞增生转录因子FoxA2的水平降低。结果表明，在这个弹性蛋白酶诱导的COPD模型中，是疾病严重程度的一个辅助因子，并突出了STAT6途径在发病机制中的相关性。
