Levitz S M, Diamond R D
J Infect Dis. 1985 Jul;152(1):33-42. doi: 10.1093/infdis/152.1.33.
Despite the critical role for neutrophils in host defenses against invasive aspergillosis, previous studies have established that neutrophils are unable to kill resting conidia of Aspergillus fumigatus. The mechanisms of resistance of the conidia were therefore investigated. Electron microscopy studies showed the fusion of phagosomes containing A. fumigatus conidia with lysosomes of the neutrophil. Resting conidia of A. fumigatus were then compared with those that had been preincubated in broth until swollen, but not germinated, as well as with blastospores of Candida albicans (two fungal forms that are killed by neutrophils) and zymosan particles. Despite comparable susceptibility to phagocytosis, resting conidia of A. fumigatus stimulated production of significantly less superoxide anion, hydrogen peroxide, and hypochlorous acid and induced less myeloperoxidase-dependent iodination by neutrophils than did the preincubated conidia of A. fumigatus, blastospores of C. albicans, or zymosan particles. In addition, resting conidia of A. fumigatus were relatively resistant to cell-free killing by oxidants presumed to be generated by neutrophils. Thus, resistance of resting conidia of A. fumigatus to neutrophil fungicidal mechanisms appears to be secondary to both failure of the conidia to stimulate an optimal respiratory burst as well as resistance of the conidia to neutrophil oxidants. However, the reversal of this resistance by preincubation of the conidia suggests that neutrophils still may form an important host defense against the conidia of A. fumigatus.
尽管中性粒细胞在宿主抵御侵袭性曲霉病中发挥着关键作用，但先前的研究已证实中性粒细胞无法杀死烟曲霉的静止分生孢子。因此，对分生孢子的抗性机制进行了研究。电子显微镜研究显示，含有烟曲霉分生孢子的吞噬体与中性粒细胞的溶酶体发生了融合。随后，将烟曲霉的静止分生孢子与在肉汤中预孵育直至肿胀但未萌发的分生孢子进行比较，同时也与白色念珠菌的芽生孢子（两种可被中性粒细胞杀死的真菌形态）和酵母聚糖颗粒进行比较。尽管对吞噬作用的敏感性相当，但与预孵育的烟曲霉分生孢子、白色念珠菌的芽生孢子或酵母聚糖颗粒相比，烟曲霉的静止分生孢子刺激中性粒细胞产生的超氧阴离子、过氧化氢和次氯酸显著减少，且诱导的髓过氧化物酶依赖性碘化作用也较少。此外，烟曲霉的静止分生孢子对假定由中性粒细胞产生的氧化剂的无细胞杀伤作用具有相对抗性。因此，烟曲霉静止分生孢子对中性粒细胞杀菌机制的抗性似乎源于分生孢子未能刺激最佳呼吸爆发以及分生孢子对中性粒细胞氧化剂的抗性。然而，分生孢子预孵育后这种抗性的逆转表明，中性粒细胞仍可能构成抵御烟曲霉分生孢子的重要宿主防御机制。
