Muriform Cells Can Reproduce by Dividing in an Athymic Murine Model of Chromoblastomycosis due to Fonsecaea pedrosoi

Muriform Cells Can Reproduce by Dividing in an Athymic Murine Model of Chromoblastomycosis due to Fonsecaea pedrosoi
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鼠形细胞可以通过在由 Fonsecaea pedrosoi 引起的着色芽生菌病的无胸腺小鼠模型中分裂来繁殖

DOI:
10.4269/ajtmh.19-0465
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发表时间:
2020-08-01
影响因子:
3.3
通讯作者:
Li, Dongsheng
Li, Dongsheng
中科院分区:
医学4区
文献类型:
--
作者:
Dong, Bilin;Liu, Wei;Li, Dongsheng

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Ponsecaea pedrosoi转化为菌落可提高宿主免疫细胞对吞噬和清除的抵抗力,并与嗜铬芽胞菌病的慢性化有关。在这里,我们的目标是通过实验的NU/NU-BALB/c小鼠模型来确定菌落样细胞是否能够在组织中繁殖而不反向转化为菌丝形式。在整个81d的观察期内,接种菌丝后75d,大部分菌丝已转化为菌落状细胞,并在接种后81d仍保持这种寄生形态,同时组织中真菌负荷增加,足底病变加重。扫描和透射电子显微镜检查表明,在组织中获得的或在体外诱导的菌落状细胞可以通过分裂产生子代细胞,同时子代细胞具有产生芽和反向生长为菌丝的潜力。胞外酶检测表明,菌落形成的胞外酶与菌丝组成的胞外酶有很大不同,但两者都具有明显的代谢活性。而环磷酰胺(50 mg/kg,隔日一次)给药后50~80d重复给药,足底大部分菌落细胞逐渐转化为细长的菌丝,未见明显的炎性细胞浸润。因此,我们推测在小鼠组织中,菌丝状细胞和菌落状细胞之间的形态转化可能与宿主的免疫状态有关。
Transformation of Fonsecaea pedrosoi into muriform cells enhances the resistance against phagocytosis and elimination by host immune cells, and links to the chronicity of chromoblastomycosis. Here, we aim to determine whether the muriform cells can reproduce in tissue without reverse transformation into hyphal form by using an experimental nu/nu-BALB/c mouse model of chromoblastomycosis due to F. pedrosoi. During the whole 81-day observation period, most of the hyphal inocula had transformed into muriform cells at 75 days postinoculation and maintained as this parasitic morphology till 81 days postinoculation simultaneously with increased fungal loads in tissue and the worsening of footpad lesion. Scanning and transmitting electronic microscope examinations showed that the muriform cells obtained in tissue or induced in vitro can reproduce daughter cells by dividing, and, meanwhile, the daughter cells had the potential to produce buds and grow into hyphae reversely. Furthermore, exoenzyme examination suggested that the profile of exoenzymes constituted by muriform cells was quite different from that constituted by hyphae although the assay showed both of them had obvious metabolic activity. By contrast, most muriform cells in the footpad gradually transformed into the elongated hyphae without obvious infiltration of inflammatory cells during repeated intraperitoneal administration of cyclophosphamide (50 mg/kg, per every other day) from 50 to 80 days postinoculation. Therefore, we infer that F. pedrosoi can reproduce by dividing as muriform cells in mouse tissue, and the morphological transformation between hyphal form and muriform cells is possibly associated with the host immune status.