据介绍,北美数百万冬眠蝙蝠死于白鼻综合征(WNS),这是一种由P.destructans入侵皮肤引起的新发疾病。P.destructans入侵蝙蝠表皮的机制尚不清楚。
通过体内观察,研究人员用新产生的棕色蝙蝠(Myotis lucifugus)角质形成细胞系模拟冬眠。研究人员发现了P.destructans的隐形细胞内生活方式,它抑制角质形成细胞的凋亡,并通两种表皮生长因子受体(EGFR)依赖的机制在细胞中传播:在休眠期间主动渗透和在觉醒期间诱导内吞作用。内吞的P.destructans的黑色素阻断了内溶酶体的成熟,促进了P.destructan在恢复休眠后的存活和发芽。
总之,这一研究表明,阻断EGFR会阻止破坏性P. destructans进入角质形成细胞。
附:英文原文
Title: Pathogenic strategies of Pseudogymnoascus destructans during torpor and arousal of hibernating bats
Author: Marcos Isidoro-Ayza, Bruce S. Klein
Issue&Volume: 2024-07-12
Abstract: Millions of hibernating bats across North America have died from white-nose syndrome (WNS), an emerging disease caused by a psychrophilic (cold-loving) fungus, Pseudogymnoascus destructans, that invades their skin. Mechanisms of P. destructans invasion of bat epidermis remain obscure. Guided by our in vivo observations, we modeled hibernation with a newly generated little brown bat (Myotis lucifugus) keratinocyte cell line. We uncovered the stealth intracellular lifestyle of P. destructans, which inhibits apoptosis of keratinocytes and spreads through the cells by two epidermal growth factor receptor (EGFR)–dependent mechanisms: active penetration during torpor and induced endocytosis during arousal. Melanin of endocytosed P. destructans blocks endolysosomal maturation, facilitating P. destructans survival and germination after return to torpor. Blockade of EGFR aborts P. destructans entry into keratinocytes.
DOI: adn5606
Source: https://www.science.org/doi/10.1126/science.adn5606