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α-葡聚糖诱导的活性氧在树突状细胞中的作用及其对结核分枝杆菌免疫反应的影响。

Role of α-glucan-induced oxygen species in dendritic cells and its impact in immune response against tuberculosis.

机构信息

IMEX-CONICET-ANM, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.

出版信息

Int J Med Microbiol. 2019 Sep;309(6):151328. doi: 10.1016/j.ijmm.2019.07.002. Epub 2019 Jul 11.

Abstract

With 10 million new cases and three million deaths estimated to occur yearly ̶ more than any time in history ̶ tuberculosis (TB) remains the single most widespread and deadly infectious disease. Until recently, it was thought that both latent and active TB was primarily related to host factors. Nonetheless, the participation of bacterial factors is becoming increasingly evident. Minimal variations in genes related to Mycobacterium tuberculosis (Mtb) virulence and pathogenesis can lead to marked differences in immunogenicity. Dendritic cells (DC) are professional antigen presenting cells whose maturation can vary depending on the cell wall composition of each particular Mtb strain being critical for the onset of the immune response against Mtb. Here we evaluated the role played by α-glucan, in the endogenous production of reactive oxygen species, ROS, and the impact on DC maturation and function. Results showed that α-glucans on Mtb induce ROS production leading to DC maturation and lymphocyte proliferation. Even more, α-glucans induced Syk activation but were not essential in non-opsonized phagocytosis. In summary, α-glucans of Mtb participates in ROS production and the subsequent DC maturation and antigen presentation, suggesting a relevant role of α-glucans for the onset of the protective immune response against TB.

摘要

每年估计有 1000 万例新发病例和 300 万人死亡——比历史上任何时候都多——结核病(TB)仍然是最广泛和最致命的传染病。直到最近,人们还认为潜伏性和活动性结核病主要与宿主因素有关。然而,细菌因素的参与越来越明显。与结核分枝杆菌(Mtb)毒力和发病机制相关的基因的微小变异可导致免疫原性的显著差异。树突状细胞(DC)是专业的抗原提呈细胞,其成熟度可根据每个特定的 Mtb 菌株的细胞壁成分而有所不同,这对于针对 Mtb 的免疫反应的开始至关重要。在这里,我们评估了α-葡聚糖在活性氧(ROS)的内源性产生中的作用,以及对 DC 成熟和功能的影响。结果表明,Mtb 上的α-葡聚糖诱导 ROS 的产生,导致 DC 的成熟和淋巴细胞的增殖。甚至,α-葡聚糖诱导了 Syk 的激活,但在非调理吞噬作用中不是必需的。总之,Mtb 的α-葡聚糖参与 ROS 的产生以及随后的 DC 成熟和抗原呈递,这表明α-葡聚糖在针对 TB 的保护性免疫反应的开始中具有重要作用。

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