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人类中性粒细胞对巴西副球孢子菌的易感性:一项超微结构和细胞化学分析。

Human neutrophils susceptibility to Paracoccidioides brasiliensis: an ultrastructural and cytochemical assay.

作者信息

Dias Maria Fernanda Reis Gavazzoni, Mesquita Jacilene, Filgueira Absalom Lima, De Souza Wanderley

机构信息

Hospital Universitário Clementino Fraga Filho, Departamento de Dermatologia, Universidade Federal do Rio de Janeiro, Brazil.

出版信息

Med Mycol. 2008 May;46(3):241-9. doi: 10.1080/13693780701824411.

DOI:10.1080/13693780701824411
PMID:18404552
Abstract

Paracoccidioidomycosis, caused by the dimorphic fungus Paracoccidioides brasiliensis, is the most prevalent systemic mycosis of Latin America, with Brazil accounting for 80% of the reported cases. The great number of neutrophils found in P. brasiliensis granulomas demonstrates the importance of polymorphonuclear neutrophils (PMN) cells during this mycotic infection. It has been found that neutrophils from healthy human donors can ingest and kill the fungus through a typical phagocytic process. The present work tests the phagocytic ability of neutrophils collected from patients that had had and were considered cured of paracoccidioidomycosis. Transmission electron microscopy and cytochemical studies indicate that patients' neutrophils eventually degenerate during phagocytosis of P. brasiliensis. Endogen peroxidase and NAD(P)H-oxidase are activated during the process showing that the respiratory burst and the neutrophil degranulation are triggered by the attachment of the yeast cells. Apparently these processes are not enough to kill P. brasiliensis. Although fungicidal activity can be determined by colony forming unit (CFU) counting, qualitative data suggest, as noted, that neutrophils from patients with treated paracoccidioidomycosis degenerate during the phagocytosis process. Hence, this work demonstrates the existence of a functional neutrophil deficiency against P. brasiliensis in susceptible individuals. The exact origin of this susceptibility is still to be determined in further studies.

摘要

副球孢子菌病由双态真菌巴西副球孢子菌引起,是拉丁美洲最常见的系统性真菌病,巴西报告的病例占80%。在巴西副球孢子菌肉芽肿中发现大量中性粒细胞,表明多形核中性粒细胞(PMN)在这种真菌感染过程中具有重要作用。研究发现,健康人类供体的中性粒细胞可通过典型的吞噬过程摄取并杀死该真菌。本研究检测了曾患副球孢子菌病且被认为已治愈的患者所采集的中性粒细胞的吞噬能力。透射电子显微镜和细胞化学研究表明,患者的中性粒细胞在吞噬巴西副球孢子菌的过程中最终会发生退化。内源性过氧化物酶和NAD(P)H氧化酶在该过程中被激活,表明呼吸爆发和中性粒细胞脱颗粒是由酵母细胞的附着触发的。显然,这些过程不足以杀死巴西副球孢子菌。虽然杀菌活性可以通过菌落形成单位(CFU)计数来确定,但定性数据表明,如前所述,接受过治疗的副球孢子菌病患者的中性粒细胞在吞噬过程中会退化。因此,本研究证明了易感个体中存在针对巴西副球孢子菌的功能性中性粒细胞缺陷。这种易感性的确切来源仍有待进一步研究确定。

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