Invasive candidiasis stimulates hepatocyte and monocyte production of active transforming growth factor β
Invasive candidiasis stimulates hepatocyte and monocyte production of active transforming growth factor β
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DOI：
10.1128/iai.69.8.5115-5120.2001
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发表时间：
2001-08-01
影响因子：
3.1
通讯作者：
Chanock, SJ
中科院分区：
文献类型：
--
作者：
Letterio, JJ;Lehrnbecher, T;Chanock, SJ
白色念珠菌是一种机会性真菌病原体，是免疫功能受损患者发病和死亡的主要原因。细胞因子对白色念珠菌侵袭组织的反应可以影响淋巴细胞和其他单核细胞的分化和功能，这些细胞是宿主反应的关键组成部分。虽然在感染白色念珠菌的小鼠中已经记录了转化生长因子β (tgf - β)的产生，并且已知其抑制吞噬细胞功能，但这种细胞因子在系统性念珠菌病发病机制中的细胞来源和作用尚不清楚。我们通过免疫组织化学研究了一种罕见的淋巴网状恶性肿瘤并发症——慢性弥散性念珠菌病（CDC）患者的组织样本，以及CDC的中性粒细胞减少兔模型，研究了tgf - β的产生来源。有记录的CDC患者的肝活检标本显示炎症性肉芽肿内细胞外基质相关tgf - β 1染色强烈，邻近肝细胞内tgf - β 1和tgf - β 3染色强烈。这些结果与使用识别成熟tgf - β蛋白的中和抗体在感染的中性粒细胞减少兔的肝脏中观察到的tgf - β 3的免疫定位相关。体外培养白色念珠菌培养的人外周血单核细胞释放大量具有生物活性的tgf - β 1。数据表明，肝细胞和受感染的单核细胞局部产生活性tgf - β是对白色念珠菌感染反应的一个组成部分，这很可能导致免疫功能受损宿主的疾病进展。
Candida albicans is an opportunistic fungal pathogen and a major cause of morbidity and mortality in patients with compromised immune function. The cytokine response to tissue invasion by C. albicans can influence the differentiation and function of lymphocytes and other mononuclear cells that are critical components of the host response. While the production of transforming growth factor beta (TGF-beta) has been documented in mice infected with C. albicans and is known to suppress phagocyte function, the cellular source and role of this cytokine in the pathogenesis of systemic candidiasis are not well understood. We have investigated the source of production of TGF-beta by immunohistochemical studies in tissue samples from patients with an uncommon complication of lymphoreticular malignancy, chronic disseminated candidiasis (CDC), and from a neutropenic-rabbit model of CDC. Liver biopsy specimens from patients with documented CDC demonstrated intense staining for extracellular matrix-associated TGF-beta1 within inflammatory granulomas, as well as staining for TGF-beta1 and TGF-beta3 within adjacent hepatocytes. These results correlate with the immunolocalization of TGF-beta3 observed in livers of infected neutropenic rabbits, using a neutralizing antibody that recognizes the mature TGF-beta protein. Human peripheral blood monocytes incubated with C. albicans in vitro release large amounts of biologically active TGF-beta1. The data demonstrate that local production of active TGF-betas by hepatocytes and by infected mononuclear cells is a component of the response to C. albicans infection that most probably contributes to disease progression in the immunocompromised host.