Zawrotniak Marcin, Satala Dorota, Juszczak Magdalena, Bras Grażyna, Rapala-Kozik Maria
Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
Doctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków, Poland.
Sci Rep. 2025 Feb 26;15(1):6946. doi: 10.1038/s41598-025-91425-x.
Candida albicans, a prevalent fungal pathogen, employs aspartyl proteases such as Sap6 to evade immune defenses, challenging our understanding of host‒pathogen interactions. This research examined the impact of Sap6 on neutrophil responses, which are crucial for innate immunity. Employing flow cytometry and fluorescence microscopy, we explored how Sap6 affects neutrophil functions, particularly by focusing on reactive oxygen species (ROS) production, neutrophil extracellular traps release (NETosis), and apoptosis. Our findings revealed Sap6's unique ability to bind and internalize in neutrophils, significantly attenuating ROS production through proteolytic damage to NADPH oxidase, resulting in blocking the ROS-dependent NETosis pathway. This disruption in neutrophil functions by Sap6 suggested the presence of a 'Trojan horse' mechanism by C. albicans. This mechanism reveals a sophisticated immune evasion strategy, shedding light on fungal pathogenicity and host immune interactions. Understanding fungal proteases in immune modulation could inspire new therapeutic approaches for fungal infections.
白色念珠菌是一种常见的真菌病原体，它利用天冬氨酸蛋白酶（如Sap6）来逃避免疫防御，这对我们理解宿主与病原体的相互作用提出了挑战。本研究考察了Sap6对中性粒细胞反应的影响，而中性粒细胞反应对先天免疫至关重要。我们运用流式细胞术和荧光显微镜，探究Sap6如何影响中性粒细胞功能，尤其着重于活性氧（ROS）生成、中性粒细胞胞外诱捕网释放（NETosis）和细胞凋亡。我们的研究结果显示，Sap6具有在中性粒细胞中结合并内化的独特能力，通过对NADPH氧化酶的蛋白水解损伤显著减弱ROS生成，从而阻断ROS依赖的NETosis途径。Sap6对中性粒细胞功能的这种干扰表明白色念珠菌存在一种“特洛伊木马”机制。这一机制揭示了一种复杂的免疫逃避策略，为真菌致病性和宿主免疫相互作用提供了新的认识。了解真菌蛋白酶在免疫调节中的作用可能会启发针对真菌感染的新治疗方法。
