A secreted pore-forming protein modulates cellular endolysosomes to augment antigen presentation
A secreted pore-forming protein modulates cellular endolysosomes to augment antigen presentation
复制标题
分泌的成孔蛋白调节细胞内溶酶体以增强抗原呈递
DOI：
10.1096/fj.202001176r
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发表时间：
2020-08-12
期刊：
影响因子：
4.8
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
--
作者：
Deng, Cheng-Jie;Liu, Long;Zhang, Yun
细菌成孔毒素气溶素样蛋白广泛分布于动植物中。新的证据支持它们在宿主先天免疫中的作用，但它们在适应性免疫中的直接作用仍然难以捉摸。在这项研究中，我们发现β - γ - cat，一种在青蛙bomina maxima中发现的气溶素样蛋白和三叶因子复合物，在树突状细胞抗原呈递过程中调节了内吞途径的几个步骤。该蛋白增强树突状细胞的抗原摄取，并积极中和细胞内吞细胞器的酸化，以促进抗原呈递。此外，在β - γ - cat的存在下，功能性外泌体样细胞外囊泡的释放大大增强。β - γ - cat的细胞作用增加了树突状细胞表面的主要组织相容性复合体（MHC） i -卵白蛋白和MHC II分子的数量以及释放的外泌体样细胞外囊泡。在β - γ - cat存在的情况下，树突状细胞对初始T细胞的抗原呈递能力增强。总的来说，这些作用导致了强烈的细胞毒性T淋巴细胞反应和抗原特异性抗体反应。我们的研究结果提供了证据，证明脊椎动物分泌的成孔蛋白可以通过直接调节细胞内吞和胞外通路来增加抗原呈递，从而导致适应性免疫的强大激活。
Bacterial pore-forming toxin aerolysin-like proteins are widely distributed in animals and plants. Emerging evidence supports their roles in host innate immunity, but their direct actions in adaptive immunity remain elusive. In this study, we found that beta gamma-CAT, an aerolysin-like protein and trefoil factor complex identified in the frogBombina maxima, modulated several steps of endocytic pathways during dendritic cell antigen presentation. The protein augmented the antigen uptake of dendritic cells and actively neutralized the acidification of cellular endocytic organelles to favor antigen presentation. In addition, the release of functional exosome-like extracellular vesicles was largely enhanced in the presence of beta gamma-CAT. The cellular action of beta gamma-CAT increased the number of major histocompatibility complex (MHC) I-ovalbumin and MHC II molecules on dendritic cell surfaces and the released exosome-like extracellular vesicles. An enhanced antigen presentation capacity of dendritic cell for priming of naive T cells was detected in the presence of beta gamma-CAT. Collectively, these effects led to strong cytotoxic T lymphocyte responses and antigen-specific antibody responses. Our findings provide evidence that a vertebrate-secreted pore-forming protein can augment antigen presentation by directly modulating cellular endocytic and exocytic pathways, leading to robust activation of adaptive immunity.