Unité des Infections Bactérienne Invasives, Institut Pasteur, Paris, France.
PLoS One. 2011;6(7):e22210. doi: 10.1371/journal.pone.0022210. Epub 2011 Jul 21.
Severe meningococcal sepsis is still of high morbidity and mortality. Its management may be improved by an experimental model allowing better understanding of its pathophysiology. We developed an animal model of meningococcal sepsis in transgenic BALB/c mice expressing human transferrin. We studied experimental meningococcal sepsis in congenic transgenic BALB/c mice expressing human transferrin by transcriptional profiling using microarray analysis of blood and brain samples. Genes encoding acute phase proteins, chemokines and cytokines constituted the largest strongly regulated groups. Dynamic bioluminescence imaging further showed high blood bacterial loads that were further enhanced after a primary viral infection by influenza A virus. Moreover, IL-1 receptor-associated kinase-3 (IRAK-3) was induced in infected mice. IRAK-3 is a negative regulator of Toll-dependant signaling and its induction may impair innate immunity and hence result in an immunocompromised state allowing bacterial survival and systemic spread during sepsis. This new approach should enable detailed analysis of the pathophysiology of meningococcal sepsis and its relationships with flu infection.
严重的脑膜炎球菌败血症仍然具有较高的发病率和死亡率。通过建立一种实验模型，可以更好地了解其病理生理学，从而改善其治疗方法。我们在表达人转铁蛋白的转基因 BALB/c 小鼠中建立了脑膜炎球菌败血症的动物模型。我们通过对血液和脑组织样本的微阵列分析，对表达人转铁蛋白的同源转基因 BALB/c 小鼠进行实验性脑膜炎球菌败血症的转录组谱研究。编码急性期蛋白、趋化因子和细胞因子的基因构成了最大的强调节群体。动态生物发光成像进一步显示血液中的细菌载量很高，在甲型流感病毒初次感染后进一步增加。此外，感染小鼠中诱导了白细胞介素 1 受体相关激酶-3（IRAK-3）。IRAK-3 是 Toll 依赖信号的负调节剂，其诱导可能会损害先天免疫，从而导致免疫功能低下，使细菌在败血症期间存活并在全身扩散。这种新方法应该能够详细分析脑膜炎球菌败血症的病理生理学及其与流感感染的关系。
