Cryptococcus neoformans and cryptococcal glucuronoxylomannan, galactoxylomannan, and mannoprotein induce different levels of tumor necrosis factor alpha in human peripheral blood mono-nuclear cells
Cryptococcus neoformans and cryptococcal glucuronoxylomannan, galactoxylomannan, and mannoprotein induce different levels of tumor necrosis factor alpha in human peripheral blood mono-nuclear cells
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DOI：
10.1128/iai.65.1.272-278.1997
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发表时间：
1997-01-01
影响因子：
3.1
通讯作者：
Hoepelman, IM
中科院分区：
文献类型：
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作者：
Chaka, W;Verheul, AFM;Hoepelman, IM
肿瘤坏死因子α（TNF-α）在新生隐球菌播散性感染期间由外周血单核细胞（PBMC）释放可启动并放大宿主的免疫应答，导致真菌的消除。四株临床分离的C.新型隐球菌，实验室菌株（NIH 37），和纯化的隐球菌组分葡糖醛酸甘露聚糖（GXM）、半乳糖基甘露聚糖（GalXM）和甘露糖蛋白（MPI和MP2）在不同调理剂条件下进行了研究。在无血清条件下，所有菌株和隐球菌组分诱导的TNF-α水平均未超过背景水平。正常人血清（NHS）增强了整个隐球菌和不同隐球菌组分的TNF-α诱导，其中MP2是最有效的TNF-α诱导剂。补体灭活（HI NHS）几乎消除了整个隐球菌和GXM诱导TNF-α的能力。相反，当MPI、MP2和GalXM分别与I-II NASI孵育时，原始TNF-α水平分别为48%、71%和44%。MP孵育与节拍灭活免疫球蛋白G（IgG）耗尽血清仍然诱导50%的TNF-α水平诱导的成分与I-II NHS孵育。这两种血清含有相同的非常低水平的抗MP IgG抗体，表明除了抗体之外的热稳定因子的调理作用。两种抗CD 14单克隆抗体（60 BCA和3C 10）抑制由MP 2诱导的TNF-α的产生。结果表明：（1）C.新生儿和GXM强烈依赖于补体，（ii）除了IG之外，MP 1和MP2对TNF-α的诱导由热稳定血清因子促进，和（iii）CD 14可能参与MP2对TNF-α的诱导。
Tumor necrosis factor alpha (TNF-alpha) release by peripheral blood mononuclear cells (PBMC) during disseminated infection by Cryptococcus neoformans may initiate and amplify the immune response of the host, leading to elimination of the fungus. The ability to induce TNF-alpha in PBMC by four clinical strains of C. neoformans, a laboratory strain (NIH 37), and the purified cryptococcal components glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoproteins (MPI and MP2) were investigated under different opsonic conditions. In the absence of serum, the levels of TNF-alpha induced hy all strains and cryptococcal components were not shove background levels. Normal human serum (NHS) enhanced TNF-alpha induction by whole cryptococci and the different cryptococcal components, with MP2 being the most potent TNF-alpha inducer. Inactivation of complement (HI NHS) almost abrogated the ability of whole cryptococci and the GXMs to induce TNF-alpha. In contrast, when MPI, MP2, and GalXM were incubated with I-II NASI 48, 71, and 44%, respectively, of the original TNF-alpha levels remained. MPs incubated with beat-inactivated immunoglobulin G (IgG)-depleted serum still induced 50% of the levels of TNF-alpha induced by components incubated with I-II NHS. Both these sera contained the same very low levels of anti-MP IgG antibodies, indicating the opsonic effect of a heat-stable factor other than antibody, Two anti-CD14 monoclonal antibodies (60BCA and 3C10) inhibited the production of TNF-alpha induced by MP2. The results indicate that (i) induction of TNF-alpha by C. neoformans and GXMs strongly depends on complement, (ii) MP1 and MP2 induction of TNF-alpha is facilitated by a heat-stable serum factor other than Ig, and (iii) CD14 mag be involved in the induction of TNF-alpha by MP2.