β-Glucan-Activated Human B Lymphocytes Participate in Innate Immune Responses by Releasing Proinflammatory Cytokines and Stimulating Neutrophil Chemotaxis.
β-Glucan-Activated Human B Lymphocytes Participate in Innate Immune Responses by Releasing Proinflammatory Cytokines and Stimulating Neutrophil Chemotaxis.
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DOI：
10.4049/jimmunol.1500559
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发表时间：
2015-12-01
期刊：
影响因子：
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通讯作者：
Carmona EM
中科院分区：
文献类型：
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作者：
Ali MF;Driscoll CB;Walters PR;Limper AH;Carmona EM
B 淋巴细胞通过感染期间产生抗体，在适应性免疫反应中发挥重要的调节作用。 B 淋巴细胞的一个鲜为人知的功能是它们能够通过刺激其表面表达的模式识别受体来直接响应感染性抗原。 β-葡聚糖是存在于许多病原真菌细胞壁中的碳水化合物，在感染期间可以在患者的外周血中检测到。它们已被证明参与先天炎症反应，因为它们可以直接激活外周巨噬细胞和树突状细胞。然而，它们作为 B 淋巴细胞直接刺激剂的作用尚未完全阐明。本研究的目的是检查 β-葡聚糖刺激 B 淋巴细胞后产生的分子机制和细胞因子谱，与成熟的 TLR-9 激动剂 CpG-寡脱氧核苷酸 (CpG) 进行比较，并研究 β-葡聚糖刺激的 B 细胞在先天免疫反应中的参与。在此，我们证明 β-葡聚糖激活的 B 淋巴细胞上调促炎细胞因子（TNFα、IL-6 和 IL-8）。有趣的是，与 CpG 不同，β-葡聚糖对 B 淋巴细胞增殖或 IgM 产生没有影响。与 CpG（TLR9 激动剂）相比，β-葡聚糖激活细胞分泌的 IL-8 水平明显更高。此外，IL-8 的分泌部分由 Dectin-1 介导，并且需要 SYK、MAPK 以及转录因子 NF-κB 和 AP-1。此外，我们观察到来自 β-葡聚糖的条件培养基刺激 B 淋巴细胞引发中性粒细胞趋化性。这些研究表明，β-葡聚糖激活的 B 淋巴细胞在真菌先天免疫反应中具有重要且新颖的作用。
B-lymphocytes play an essential regulatory role in the adaptive immune response through antibody production during infection. A less known function of B-lymphocytes is their ability to respond directly to infectious antigens through stimulation of pattern recognition receptors expressed on their surfaces. β-glucans are carbohydrates present in the cell wall of many pathogenic fungi that can be detected in the peripheral blood of patients during infection. They have been shown to participate in the innate inflammatory response as they can directly activate peripheral macrophages and dendritic cells. However, their effect as direct stimulators of B-lymphocytes has not been yet fully elucidated. The aim of this study was to examine the molecular mechanisms and cytokine profiles generated following β-glucan stimulation of B-lymphocytes, compared with the well-established TLR-9 agonist CpG-oligodeoxynucleotide (CpG) and study the participation of β-glucan stimulated B-cells in the innate immune response. Herein, we demonstrate that β-glucan activated B-lymphocytes upregulate pro-inflammatory cytokines (TNFα, IL-6 and IL-8). Interestingly, β-glucan, unlike CpG, had no effect on B-lymphocyte proliferation or IgM production. When compared with CpG (TLR9 agonist), β-glucan-activated cells secreted significantly higher levels of IL-8. Furthermore, IL-8 secretion was partially mediated by Dectin-1 and required SYK, MAPKs and the transcription factors NF-κB and AP-1. Moreover, we observed that conditioned media from β-glucan stimulated B-lymphocytes elicited neutrophil chemotaxis. These studies suggest that β-glucan activated B-lymphocytes have an important and novel role in fungal innate immune responses.