In innate immunity, macrophages play critical roles in defending against pathogens via the lysosomal degradation function of autophagy. Two distinct autophagy pathways have been identified in decades: canonical autophagy (referred to as autophagy) and LC3-associated phagocytosis (LAP). Since several conflicting findings about the anti-Candida capability of autophagy (or LAP) have been reported, they serve as the foe or friend for Candida survival is still unclearly. The current study showed that the fungicidal process of THP-1-derived macrophages (THP-1-MФ) against Candida albicans is divided into three stages as follows, the early stage (the first 12 h, increasing in the killing capability), the mid-stage (12–24 h, no change in killing capability), and the late stage (24–48 h, decreasing of the killing capability). Autophagic protein LC3B-II reached the peak in THP-1-MФ after 24 h inoculated either with C.albicans or whole glucan particles (WGP). Thus, both anti-Candida roles of autophagy and the LAP pathway have been detected at the mid-stage. For autophagy, after 24 h inoculation with C.albicans, ULK1 increased, but p-ATG13(s318) decreased obviously in THP-1-MФ, and the killing assay showed that autophagy is unhelpful for Candida killing capability. For the LAP pathway, Rubicon and ROS raised significantly in THP-1-MФ after 24 h inoculated with C.albicans; each inhibition would sharply cut down the LC3B-II accumulation, which indicated that LAP had been induced. However, mCherry-GFP-LC3 fluorescent assay exhibited that LAP phago-lysosomal fusion has been blocked, and Rubicon knockdown facilitated the Candida killing activity. These data indicated that autophagy presented as redundant to Candida defense, and LAP phago-lysosomal fusion obstruction impairs the Candida killing capability of THP-1-MФ at the mid-stage. That may explain the no change in Candida killing capability at the mid-stage.

在先天免疫中，巨噬细胞通过自噬的溶酶体降解功能在防御病原体方面发挥着关键作用。几十年来已经确定了两种不同的自噬途径：典型自噬（称为自噬）和 LC3 相关吞噬作用（LAP）。由于关于自噬（或 LAP）的抗念珠菌能力的一些相互矛盾的发现已被报道，因此它们对于念珠菌生存是敌人还是朋友仍不清楚。目前研究表明，THP-1源性巨噬细胞（THP-1-MФ）对白色念珠菌的杀菌过程分为三个阶段：早期（第12 h，杀灭能力增强）、后期（第12 h，杀灭能力增强）。中期（12-24小时，杀伤能力无变化）和晚期（24-48小时，杀伤能力下降）。在接种白色念珠菌或全葡聚糖颗粒 (WGP) 24 小时后，THP-1-MФ 中的自噬蛋白 LC3B-II 达到峰值。因此，自噬和 LAP 途径的抗念珠菌作用已在中期被检测到。自噬方面，接种C.albicans 24 h后，THP-1-MФ中ULK1升高，但p-ATG13(s318)明显降低，杀伤实验表明自噬对念珠菌杀伤能力无帮助。对于LAP途径，接种白色念珠菌24小时后，THP-1-MФ中的Rubicon和ROS显着升高；每次抑制都会急剧减少 LC3B-II 的积累，这表明 LAP 已被诱导。然而，mCherry-GFP-LC3 荧光检测显示 LAP 吞噬-溶酶体融合已被阻断，并且 Rubicon 敲低促进了念珠菌杀灭活性。这些数据表明，自噬对于念珠菌防御来说是多余的，并且LAP吞噬-溶酶体融合阻碍损害了THP-1-MФ在中期的念珠菌杀灭能力。这或许可以解释中期念珠菌杀灭能力没有变化的原因。