Weiser Jeffrey N, Roche Aoife M, Hergott Christopher B, LaRose Meredith I, Connolly Tarah, Jorgensen William L, Leng Lin, Bucala Richard, Das Rituparna
Department of Microbiology.
Department of Microbiology Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
J Infect Dis. 2015 Nov 15;212(10):1677-82. doi: 10.1093/infdis/jiv262. Epub 2015 May 5.
Mortality from pneumococcal pneumonia remains high despite antibiotic therapy, highlighting the pathogenic potential for host inflammation. We demonstrate that macrophage migration inhibitory factor (MIF), an innate immune mediator, is detrimental for survival and associated with lung pathology, inflammatory cellular infiltration, and bacterial replication in a mouse model of pneumococcal pneumonia, despite being necessary for clearance from the nasopharynx. Treatment of animals with a small-molecule inhibitor of MIF improves survival by reducing inflammation and improving bacterial control. Our work demonstrates that MIF modulates beneficial versus detrimental inflammatory responses in the host-pneumococcal interaction and is a potential target for therapeutic modulation.
尽管使用了抗生素治疗，但肺炎球菌肺炎导致的死亡率仍然很高，这突出了宿主炎症的致病潜力。我们证明，巨噬细胞移动抑制因子（MIF）作为一种先天性免疫介质，在肺炎球菌肺炎小鼠模型中对生存有害，并与肺部病理、炎性细胞浸润和细菌复制相关，尽管它对于从鼻咽部清除病原体是必需的。用MIF的小分子抑制剂治疗动物可通过减轻炎症和改善细菌控制来提高生存率。我们的研究表明，MIF在宿主-肺炎球菌相互作用中调节有益和有害的炎症反应，是治疗调节的一个潜在靶点。
