Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Infect Immun. 2011 Feb;79(2):858-66. doi: 10.1128/IAI.00466-10. Epub 2010 Dec 6.
The role of mouse peptidoglycan recognition protein PGLYRP-1 in innate immunity against Listeria monocytogenes infection was studied. The recombinant mouse PGLYRP-1 and a polyclonal antibody specific to PGLYRP-1 were prepared. The mouse PGLYRP-1 showed antibacterial activities against L. monocytogenes and other Gram-positive bacteria. PGLYRP-1 mRNA expression was induced in the spleens and livers of mice infected with L. monocytogenes. The viable bacterial number increased, and the production of cytokines such as gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) was reduced in mice when mice had been injected with anti-PGLYRP-1 antibody before infection. The levels of IFN-γ and TNF-α titers in the organs were higher and the viable bacterial number was reduced in mice injected with recombinant mouse PGLYRP-1 (rmPGLYRP-1) before infection. PGLYRP-1 could directly induce these cytokines in spleen cell cultures. The elimination of intracellular bacteria was upregulated in NMuLi hepatocyte cells overexpressing PGLYRP-1. The enhancement of the elimination of L. monocytogenes from the organs was observed in IFN-γ(-/-) mice by rmPGLYRP-1 administration but not in TNF-α(-/-) mice. These results suggest that PGLYRP-1 plays a role in innate immunity against L. monocytogenes infection by inducing TNF-α.
本研究旨在探讨鼠肽聚糖识别蛋白 PGLYRP-1 在抗李斯特菌感染固有免疫中的作用。制备了重组鼠 PGLYRP-1 和针对 PGLYRP-1 的多克隆抗体。鼠 PGLYRP-1 对李斯特菌和其他革兰氏阳性菌具有抗菌活性。李斯特菌感染小鼠的脾脏和肝脏中 PGLYRP-1 mRNA 表达上调。在感染前注射抗-PGLYRP-1 抗体的小鼠中,活菌数增加,γ干扰素(IFN-γ)和肿瘤坏死因子α(TNF-α)等细胞因子的产生减少。感染前注射重组鼠 PGLYRP-1(rmPGLYRP-1)的小鼠中,IFN-γ 和 TNF-α 效价的水平升高,活菌数减少。PGLYRP-1 可直接诱导脾细胞培养物中这些细胞因子的产生。在过表达 PGLYRP-1 的 NMuLi 肝细胞中,可增强对李斯特菌的胞内菌的清除。通过 rmPGLYRP-1 给药可增强 IFN-γ(-/-)小鼠而不是 TNF-α(-/-)小鼠对器官中李斯特菌的清除。这些结果表明 PGLYRP-1 通过诱导 TNF-α 发挥对李斯特菌感染固有免疫的作用。