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CD23 Mediates Antimycobacterial Activity of Human Macrophages

机译:CD23介导人类巨噬细胞的抗分枝杆菌活性。

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Engagement of surface receptors contributes to the antimicrobial activity of human immune cells. We show here that infection of human monocyte-derived macrophages (MDM) with live Mycobacterium avium induced the expression of CD23 on their membrane. Subsequent cross-linking of surface CD23 by appropriate ligands induced a dose-dependent antibacterial activity of MDM and the elimination of most infected cells. The stimulation of inducible nitric oxide synthase-dependent generation of NO from MDM after CD23 activation played a major role during their anti-M. avium activity. CD23 activation also induced tumor necrosis factor alpha (TNF-α) production from MDM. Mycobacteria reduction was partially inhibited by the addition of neutralizing anti-TNF-α antibody to cell cultures without affecting NO levels, which suggested the role of this cytokine for optimal antimicrobial activity. Finally, interleukin-10, a Th2 cytokine known to downregulate CD23 pathway, is shown to decrease NO generation and mycobacteria elimination by macrophages. Therefore, (i) infection with M. avium promotes functional surface CD23 expression on human macrophages and (ii) subsequent signaling of this molecule contributes to the antimicrobial activity of these cells through an NO- and TNF-α-dependent pathway. This study reveals a new human immune response mechanism to counter mycobacterial infection involving CD23 and its related ligands.
机译:表面受体的参与有助于人类免疫细胞的抗菌活性。我们在这里显示活人鸟分枝杆菌感染人单核细胞衍生的巨噬细胞(MDM)诱导CD23在其膜上的表达。随后通过合适的配体进行的表面CD23交联诱导了MDM的剂量依赖性抗菌活性,并消除了大多数感染细胞。 CD23激活后,MDM对可诱导型一氧化氮合酶依赖性NO的刺激在其抗M过程中起主要作用。鸟卵活动。 CD23激活还诱导了MDM产生肿瘤坏死因子α(TNF-α)。通过向细胞培养物中添加中和性抗TNF-α抗体可部分抑制分枝杆菌的减少,而不会影响NO的水平,这表明该细胞因子具有最佳抗菌活性。最后,白细胞介素10(一种已知下调CD23途径的Th2细胞因子)显示可减少NO的产生和巨噬细胞对分枝杆菌的消除。因此,(i)用 M感染。鸟卵促进人巨噬细胞表面功能性CD23的表达,(ii)该分子的后续信号通过NO和TNF-α依赖性途径促进这些细胞的抗菌活性。这项研究揭示了一种新的人类免疫反应机制,以对抗涉及CD23及其相关配体的分枝杆菌感染。

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