Colonial morphotype as a determinant of cytokine expression by human monocytes infected with Mycobacterium avium.
Colonial morphotype as a determinant of cytokine expression by human monocytes infected with Mycobacterium avium.
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DOI：
10.4049/jimmunol.150.7.2945
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发表时间：
1993-04
影响因子：
4.4
通讯作者：
H. Shiratsuchi;Z. Toossi;Mark A. Mettler;J. Ellner
中科院分区：
文献类型：
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作者：
H. Shiratsuchi;Z. Toossi;Mark A. Mettler;J. Ellner
鸟分枝杆菌是一种细胞内病原体，可引起艾滋病患者的播散性感染。菌落形态型（光滑透明（SmT）与光滑圆顶（SmD））是小鼠毒力和人单核细胞复制能力的关键决定因素。一些细胞因子（IL-1和IL-6）促进，而其他细胞因子（IFN-γ和TNF）抑制细胞内M。鸟类生长对决定M.然而，Avium并不清楚。在这项研究中，我们研究了细胞因子表达的人单核细胞刺激的同基因克隆分离的M。avium从健康供体制备单核细胞，并与或不与同基因M培养。Avium长达7天。使用ELISA通过免疫测定法测量单核细胞上清液和细胞裂解物中的细胞因子水平（IL-1、IL-6和TNF-α）。M.也通过提取总RNA并对其进行北方印迹分析来确定鸟类。最佳细胞因子释放出现在24 h。SmD在上清液中诱导的以下细胞因子水平高于SmT：IL-1 alpha（140 +/- 32（平均值+/- SE）vs 47 +/- 16 pg/ml，p < 0.02），IL-1 β（4.0 +/- 0.9 vs 1.7 +/- 0.5 ng/ml，p < 0.01）和TNF-α（2725 +/- 546 vs 1464 +/- 409 pg/ml，p < 0.01）。两种菌株的IL-6产量相当。SmD和SmT分离株诱导IL-1 β、TNF和IL-6的稳态mRNA水平相当。脉冲追踪分析表明，SmT和SmD之间的细胞因子表达的差异发生在单核细胞裂解物在最早的时间点（脉冲标记后立即）。特异性mRNA的表达与IL-1和TNF的产生的解离表明，某些细胞因子表达的翻译能力被毒性更强的SmT降低。细胞因子的差异诱导可能是M.从艾滋病患者中分离的禽流感病毒株。
Mycobacterium avium is an intracellular pathogen that causes disseminated infection in patients with AIDS. Colonial morphotype (smooth-transparent (SmT) vs smooth-domed (SmD)) is a key determinant of virulence in mice and the capacity for replication in human monocytes. Some cytokines (IL-1 and IL-6) promote, whereas others (IFN-gamma and TNF) inhibit intracellular M. avium growth. The specific factors that determine virulence of M. avium, however, are not clear. In this study, we examined cytokine expression by human monocytes stimulated with isogeneic cloned isolates of M. avium. Monocytes were prepared from healthy donors and cultured with or without isogeneic M. avium for up to 7 days. Cytokine levels (IL-1, IL-6, and TNF-alpha) in monocyte supernatants and cell lysates were measured by immunoassay using an ELISA. The expression of cytokine mRNA by monocytes infected with M. avium also was determined by extracting total RNA and subjecting it to Northern blot analysis. Optimal cytokine release occurred at 24 h. SmD induced higher levels of the following cytokines in supernatants than SmT: IL-1 alpha (140 +/- 32 (mean +/- SE) vs 47 +/- 16 pg/ml, p < 0.02), IL-1 beta (4.0 +/- 0.9 vs 1.7 +/- 0.5 ng/ml, p < 0.01), and TNF-alpha (2725 +/- 546 vs 1464 +/- 409 pg/ml, p < 0.01). IL-6 production was comparable for both strains. SmD and SmT isolates induced comparable levels of steady state mRNA for IL-1 beta, TNF, and IL-6. Pulse-chase analysis indicated that differences in cytokine expression between SmT and SmD occurred in monocyte lysates at the earliest time point (immediately after pulse-labeling). The dissociation of the expression of specific mRNA from production of IL-1 and TNF suggests that translational capacity for the expression of certain cytokines was reduced by the more virulent SmT. Differential induction of cytokine may be a factor in the pathogenicity of M. avium strains isolated from patients with AIDS.