TRAF3 gene regulates macrophage migration and activation by lung epithelial cells infected with Aspergillus fumigatus

作者：Shumi Shang, Dan He, Cong Liu, X. Bao, Shuaishuai Han, Li Wang · 发表于：Microbiology Spectrum · 年份：2023 · DOI：10.1128/spectrum.02699-23 · 被引用次数：4 · 研究领域：NF-κB Signaling Pathways、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Ocular Infections and Treatments

ABSTRACT Aspergillus fumigatus is an opportunistic pathogen that infects immunocompromised patients and imposes a heavy burden on global health. Searching for key genes in host resistance to A. fumigatus infection can help us understand the mechanisms of A. fumigatus -host interactions and provide new targets for the treatment of fungal infections. TRAF3 is one of the intracellular adapter proteins of the innate immune response that regulates signaling in various cellular processes, including host defense against pathogens. However, the defense mechanism of TRAF3 against A. fumigatus infection remains unknown. In this study, we found that TRAF3 overexpression led to the adhesion and internalization of more spores of A. fumigatus in lung epithelial cells and thus greater host immune surveillance evasion. Meanwhile, TRAF3 was able to regulate the expression of pro-inflammatory cytokines in lung epithelial cells infected with A. fumigatus through the negative regulation of NF-κB and MAPK signaling pathways. In this study, we also examined the effects of TRAF3 in the interaction between lung epithelial cells, macrophages, and A. fumigatus spores, and the results showed that TRAF3-overexpressing lung epithelial cells reduced the migration and activation of macrophages after A. fumigatus infection. In vivo experiments using TRAF3-overexpressing transgenic zebrafish larvae revealed that TRAF3 overexpression increased the fungal load and mortality of zebrafish infected with A. fumiga...