Institute of Immunology and Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China;
Institute of Immunology and Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China;
J Immunol. 2014 Aug 1;193(3):1133-41. doi: 10.4049/jimmunol.1303303. Epub 2014 Jun 20.
A protective effect induced by bacterial preinfection upon a subsequent lethal influenza virus infection has been observed, but the underlying immune mechanisms have not yet been fully elucidated. In this study, we used a mouse model of Klebsiella pneumoniae preinfection to gain insight into how bacterial preinfection influences the subsequent lethal influenza virus infection. We found that K. pneumoniae preinfection significantly attenuated lung immune injury and decreased mortality during influenza virus infection, but K. pneumoniae-specific immunity was not involved in this cross-protection against influenza virus. K. pneumoniae preinfection limited NK cell expansion, which was involved in influenza-induced immune injury and death. Furthermore, K. pneumoniae preinfection could not control NK cell expansion and death during influenza virus infection in Rag1(-/-) mice, but adoptive transfer of T cells from wild-type mice was able to restore this protective effect. Our data suggest that the adaptive immune response activated by bacterial infection limits the excessive innate immune response induced by a subsequent influenza infection, ultimately protecting mice from death.
细菌预先感染对随后的致死性流感病毒感染产生的保护作用已被观察到,但潜在的免疫机制尚未完全阐明。在本研究中,我们使用肺炎克雷伯菌预先感染的小鼠模型来深入了解细菌预先感染如何影响随后的致死性流感病毒感染。我们发现,肺炎克雷伯菌预先感染显著减轻了流感病毒感染期间的肺部免疫损伤和死亡率,但肺炎克雷伯菌特异性免疫并不参与这种对流感病毒的交叉保护。肺炎克雷伯菌预先感染限制了 NK 细胞的扩增,而 NK 细胞的扩增参与了流感引起的免疫损伤和死亡。此外,在 Rag1(-/-)小鼠中,肺炎克雷伯菌预先感染不能控制流感病毒感染期间 NK 细胞的扩增和死亡,但从野生型小鼠中过继转移 T 细胞能够恢复这种保护作用。我们的数据表明,细菌感染激活的适应性免疫反应限制了随后流感感染引起的过度固有免疫反应,最终使小鼠免于死亡。