Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Linköping University, Sweden.
Hum Immunol. 2010 Jun;71(6):535-40. doi: 10.1016/j.humimm.2010.02.022. Epub 2010 Mar 11.
Mycobacterium tuberculosis (Mtb) manipulates cells of the innate immune system to provide the bacteria with a sustainable intracellular niche. Mtb spread through aerosol carrying them deep into the lungs, where they are internalized by phagocytic cells, such as neutrophils (PMNs), dendritic cells (DCs), and macrophages. PMNs undergo accelerated apoptosis after interaction with the bacterium, and apoptotic cells are sequestered by neighboring phagocytes. Removal of aged apoptotic cells because of natural tissue turnover is described as an immunologically silent process facilitating resolution of inflammation and inhibition of DC maturation. Silencing of immune cells could be favorable for intracellular bacteria. The aim of this study was to clarify the interaction between Mtb-induced apoptotic PMNs and DCs, and evaluate whether this interaction follows the proposed anti-inflammatory pathway. In contrast to aged apoptotic cells, Mtb-induced apoptotic PMNs induced functional DC maturation. We found that the cell fraction from Mtb-induced apoptotic PMNs contained almost all stimulatory capacity, suggesting that cell-cell interaction is crucial for DC activation. Inhibitory studies showed that this cell contact-dependent activation required binding of the PMN Mac-1 (CD11b/CD18) to the DC via DC-SIGN and endocytic activity involving the alpha(v)beta(5) but did not involve the scavenger receptor CD36. Taken together, this study demonstrates that the DCs can distinguish between normal and infected apoptotic PMNs via cellular crosstalk, where the DCs can sense the presence of danger on the Mtb-infected PMNs and modulate their response accordingly.
结核分枝杆菌 (Mtb) 操纵先天免疫系统的细胞，为细菌提供可持续的细胞内小生境。Mtb 通过携带它们的气溶胶传播到肺部深处，在那里被吞噬细胞（如中性粒细胞 (PMN)、树突状细胞 (DC) 和巨噬细胞）内化。PMN 与细菌相互作用后会加速凋亡，凋亡细胞被邻近的吞噬细胞隔离。由于自然组织更新而清除衰老的凋亡细胞被描述为一种免疫沉默过程，有利于炎症的解决和 DC 成熟的抑制。免疫细胞的沉默可能对细胞内细菌有利。本研究旨在阐明 Mtb 诱导的凋亡 PMN 与 DC 之间的相互作用，并评估这种相互作用是否遵循拟议的抗炎途径。与衰老的凋亡细胞相反，Mtb 诱导的凋亡 PMN 诱导功能性 DC 成熟。我们发现，Mtb 诱导的凋亡 PMN 的细胞部分几乎包含了所有的刺激能力，这表明细胞间相互作用对于 DC 激活至关重要。抑制研究表明，这种细胞接触依赖性激活需要 PMN Mac-1 (CD11b/CD18) 通过 DC-SIGN 与 DC 结合，以及涉及 alpha(v)beta(5) 的内吞活性，但不涉及清道夫受体 CD36。总之，这项研究表明，DC 可以通过细胞串扰区分正常和感染的凋亡 PMN，在这种串扰中，DC 可以感知 Mtb 感染的 PMN 上存在危险，并相应地调节它们的反应。
