Tumor necrosis factor-inducing activities of Cryptococcus neoformans components
Tumor necrosis factor-inducing activities of Cryptococcus neoformans components
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DOI：
10.1128/iai.64.12.5199-5204.1996
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发表时间：
1996-12-01
影响因子：
3.1
通讯作者：
Teti, G
中科院分区：
文献类型：
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作者：
Delfino, D;Cianci, L;Teti, G
新型隐球菌诱导的肿瘤坏死因子α（TNF-α）的产生可能导致艾滋病患者的人类免疫缺陷病毒复制增加。为了鉴定主要负责刺激TNF产生的隐球菌组分，将各种浓度的葡糖醛酸甘露聚糖（GXM）、半乳糖基甘露聚糖（GalXM）、甘露糖蛋白（MP）和β（1-3）葡聚糖添加到全血培养物中。所有测试的隐球菌成分，以及整个热灭活隐球菌，都能够以剂量依赖性方式诱导TNF-α释放。MP在刺激TNF-α产生方面显著强于任何其他测试的隐球菌组分或热灭活隐球菌（P < 0.05）。GXM的活性明显低于GalXM或MP（P < 0.05）。只要每毫升0.5 μ g的MP就足以产生中等但显著的TNF-α释放升高。MP诱导的最大TNF-α水平与沙门氏菌脂多糖（我们的阳性对照）诱导的水平相似。使用分离的白细胞进行的进一步实验表明，单核细胞是主要负责TNF-α产生的细胞群，尽管不能排除其他细胞类型的参与。补体充足血浆的存在是GXM、GalXM和低剂量MP诱导TNF-α的必要条件。高MP浓度（100 μ g/ml）也能够刺激TNF-α的产生，在没有血浆的情况下。这些数据表明，C.新生儿能够诱导人白细胞中的TNF-α分泌。这可能与临床有关，因为在感染了C.新人类
Cryptococcus neoformans-induced tumor necrosis factor alpha (TNF-alpha) production may lead to increased human immunodeficiency virus replication in patients with AIDS. In order to identify cryptococcal components that are predominantly responsible for stimulating TNF production, various concentrations of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), mannoproteins (MP), and beta(1-3) glucan were added to whole-blood cultures. All of the cryptococcal components tested, as well as whole heat-killed cryptococci, were capable of inducing TNF-alpha release in a dose-dependent manner. MP were significantly more potent than any of the other cryptococcal components tested or heat-killed cryptococci in stimulating TNF-alpha production (P < 0.05). GXM, in contrast, was significantly less potent in this activity than either GalXM or MP (P < 0.05). As little as 0.5 mu g of MP per ml was sufficient to produce moderate but significant elevations of TNF-alpha release. Maximal MP-induced TNF-alpha levels were similar to those induced by Salmonella enteritidis lipopolysaccharide, our positive control. Further experiments using isolated leukocytes suggested that monocytes were the cell population mainly responsible for TNF-alpha production, although the participation of other cell types could not be excluded. The presence of complement-sufficient plasma was a necessary requirement for TNF-alpha induction by GXM, GalXM, and low doses of MP. High MP concentrations (100 mu g/ml) were also capable of stimulating TNF-alpha production in the absence of plasma. These data indicate that soluble products released by C. neoformans are capable of inducing TNF-alpha secretion in human leukocytes. This may be clinically relevant, since high concentrations of such products are frequently found in the body fluids of AIDS patients infected with C. neoformans.