Early Activation of iNKT Cells Increased Survival Time of BALB/c Mice in a Murine Model of Melioidosis
Early Activation of iNKT Cells Increased Survival Time of BALB/c Mice in a Murine Model of Melioidosis
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DOI：
10.1128/iai.00268-22
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发表时间：
2022-11
影响因子：
3.1
通讯作者：
Thitinan Kasetthat;Ludthawun Kamuthachad;R. Sermswan;H. Watarai;P. Matangkasombut;S. Wongratanacheewin
中科院分区：
文献类型：
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作者：
Thitinan Kasetthat;Ludthawun Kamuthachad;R. Sermswan;H. Watarai;P. Matangkasombut;S. Wongratanacheewin
类鼻疽是由类鼻疽伯克霍尔德杆菌引起的传染病。据报道，幼鼠体内的高干扰素γ (IFN-γ) 水平可介导针对类鼻疽伯克氏菌感染的保护作用。摘要 类鼻疽是由类鼻疽伯克霍尔德菌引起的传染病。据报道，幼鼠体内的高干扰素γ (IFN-γ) 水平可介导针对类鼻疽伯克氏菌感染的保护作用。不变的自然杀伤 T (iNKT) 细胞可以产生和分泌多种细胞因子，包括 IFN-γ。当iNKT细胞敲除（KO）BALB/c小鼠感染类鼻疽杆菌时，其存活时间明显短于野生型小鼠。感染前 24 小时，用 α-半乳糖苷神经酰胺 (α-GalCer)（一种 iNKT 细胞激活剂）腹腔内预处理未处理的 BALB/c 小鼠，早期存活率为 62.5%，与未预处理的感染对照小鼠相比，存活时间更长（分别为 14 ± 1 天和 6 ± 1 天）。注射 α-GalCer 后 4 小时，治疗小鼠的血清 IFN-γ、白细胞介素 4 (IL-4)、IL-10 和 IL-12 水平显着高于对照小鼠。有趣的是，α-GalCer预处理组的IFN-γ水平在感染后4、24和48小时下降，而对照组则大幅上升。 α-GalCer 组感染后 24 小时，血液（无生长且 1,780.00 ± 51.21，P < 0.0001）、脾脏（无生长且 34,300 ± 1,106.04，P < 0.0001）和肝脏（1,550 ± 68.72 和13,400 ± 1,066.67，P < 0.0001）比对照组高，但肺部没有（15,300 ± 761.10 和 1,320 ± 41.63，P < 0.0001），并且在感染后 48 小时几乎全部呈阴性。这项研究首次表明，α-GalCer 早期激活 iNKT 细胞有助于清除鼻疽伯克氏菌并延长小鼠的存活时间。
Melioidosis is an infectious disease caused by Burkholderia pseudomallei. High interferon gamma (IFN-γ) levels in naive mice were reported to mediate protection against B. pseudomallei infection. ABSTRACT Melioidosis is an infectious disease caused by Burkholderia pseudomallei. High interferon gamma (IFN-γ) levels in naive mice were reported to mediate protection against B. pseudomallei infection. Invariant natural killer T (iNKT) cells can produce and secrete several cytokines, including IFN-γ. When iNKT cell-knockout (KO) BALB/c mice were infected with B. pseudomallei, their survival time was significantly shorter than wild-type mice. Naive BALB/c mice pretreated intraperitoneally with α-galactosylceramide (α-GalCer), an iNKT cell activator, 24 h before infection demonstrated 62.5% survival at the early stage, with prolonged survival time compared to nonpretreated infected control mice (14 ± 1 days versus 6 ± 1 days, respectively). At 4 h after injection with α-GalCer, treated mice showed significantly higher levels of serum IFN-γ, interleukin-4 (IL-4), IL-10, and IL-12 than control mice. Interestingly, the IFN-γ levels in the α-GalCer-pretreated group were decreased at 4, 24, and 48 h after infection, while they were highly increased in the control group. At 24 h postinfection in the α-GalCer group, bacterial loads were significantly lower in blood (no growth and 1,780.00 ± 51.21, P < 0.0001), spleens (no growth and 34,300 ± 1,106.04, P < 0.0001), and livers (1,550 ± 68.72 and 13,400 ± 1,066.67, P < 0.0001) than in the control group, but not in the lungs (15,300 ± 761.10 and 1,320 ± 41.63, P < 0.0001), and almost all were negative at 48 h postinfection. This study for the first time shows that early activation of iNKT cells by α-GalCer helps clearance of B. pseudomallei and prolongs mouse survival.