Selective receptor blockade during phagocytosis does not alter the survival and growth of Mycobacterium tuberculosis in human macrophages.
Selective receptor blockade during phagocytosis does not alter the survival and growth of Mycobacterium tuberculosis in human macrophages.
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DOI：
10.1165/ajrcmb.15.6.8969271
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发表时间：
1996-12
影响因子：
6.4
通讯作者：
S. Zimmerli;S. Edwards;J. Ernst
中科院分区：
文献类型：
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作者：
S. Zimmerli;S. Edwards;J. Ernst
结核分枝杆菌在人类巨噬细胞内存活并复制，但结核杆菌抵抗杀伤的机制尚不完全清楚。我们测试了一般模型，其中结核分枝杆菌通过无法激活细胞杀菌活性的受体进入幼稚巨噬细胞来逃避杀伤。用单克隆抗体阻断补体受体类型 1 (CR1)、3 (CR3) 和 4 (CR4)，并用竞争性配体甘露糖化牛血清白蛋白 (MBSA) 阻断甘露糖受体。在存在阻断剂（引导与未阻断的受体结合）的情况下吞噬细菌后，评估结核分枝杆菌（Erdman）的存活和复制。尽管来自不同供体的单核细胞来源的巨噬细胞中的毒力结核分枝杆菌的生长速率存在显着差异，但无论用于结合和吞噬作用的受体如何，分枝杆菌的细胞内存活和复制都是相同的。我们得出的结论是，结核分枝杆菌逃避人类巨噬细胞杀伤的机制独立于受体介导的进入途径，并且按照所有进入途径共有的一个或多个步骤进行操作。联合阻断补体和甘露糖受体并不能完全消除结核分枝杆菌与巨噬细胞的结合。然而，我们发现两种聚阴离子清道夫受体配体表现出浓度依赖性的阻断结核分枝杆菌与巨噬细胞结合的能力。此外，阻断 A 类清道夫受体几乎消除了阻断补体和甘露糖受体后持续存在的所有结合。这表明 A 类清道夫受体是结核分枝杆菌-巨噬细胞相互作用的定量重要介质。结核分枝杆菌已经进化出多种机制来促进其有效进入巨噬细胞。这表明生物体通过巨噬细胞的传递可能是结核病发病机制中重要的早期步骤。
Mycobacterium tuberculosis survives and replicates within human macrophages, but the mechanisms whereby tubercle bacilli resist killing are incompletely understood. We tested the general model in which M. tuberculosis evades killing by entering naive macrophages through receptors that are unable to activate cellular microbicidal activities. Complement receptor types 1 (CR1), 3 (CR3), and 4 (CR4) were blocked with monoclonal antibodies, and mannose receptors were blocked with a competitive ligand, mannosylated bovine serum albumin (MBSA). Survival and replication of M. tuberculosis (Erdman) were evaluated after the bacteria were phagocytosed in the presence of blocking agents (directing binding to the unblocked receptors). Although there was significant variation in the growth rate of virulent M. tuberculosis in monocyte-derived macrophages from different donors, the intracellular survival and replication of mycobacteria were equivalent regardless of the receptor(s) used for binding and phagocytosis. We conclude that the mechanisms whereby M. tuberculosis evades killing by human macrophages are independent of the receptor-mediated route of entry, and operate at one or more steps common to all entry pathways. Blocking complement and mannose receptors in combination did not completely abrogate binding of M. tuberculosis to macrophages. However, we found that two polyanionic scavenger-receptor ligands exhibited a concentration-dependent ability to block binding of M. tuberculosis to macrophages. Moreover, blocking class A scavenger receptors abrogated nearly all binding that persisted after blocking complement and mannose receptors. This indicates that class A scavenger receptors are quantitatively important mediators of M. tuberculosis-macrophage interactions. M. tuberculosis has evolved multiple mechanisms to promote its efficient entry into macrophages. This suggests that passage of the organism through macrophages may be an essential early step in the pathogenesis of tuberculosis.