Center for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, The Netherlands.
PLoS Negl Trop Dis. 2010 Feb 16;4(2):e605. doi: 10.1371/journal.pntd.0000605.
Macrophage migration inhibitory factor (MIF) has emerged as a pivotal mediator of innate immunity and has been shown to be an important effector molecule in severe sepsis. Melioidosis, caused by Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast-Asia. We aimed to characterize the expression and function of MIF in melioidosis.
MIF expression was determined in leukocytes and plasma from 34 melioidosis patients and 32 controls, and in mice infected with B. pseudomallei. MIF function was investigated in experimental murine melioidosis using anti-MIF antibodies and recombinant MIF. Patients demonstrated markedly increased MIF mRNA leukocyte and MIF plasma concentrations. Elevated MIF concentrations were associated with mortality. Mice inoculated intranasally with B. pseudomallei displayed a robust increase in pulmonary and systemic MIF expression. Anti-MIF treated mice showed lower bacterial loads in their lungs upon infection with a low inoculum. Conversely, mice treated with recombinant MIF displayed a modestly impaired clearance of B. pseudomallei. MIF exerted no direct effects on bacterial outgrowth or phagocytosis of B. pseudomallei.
MIF concentrations are markedly elevated during clinical melioidosis and correlate with patients' outcomes. In experimental melioidosis MIF impaired antibacterial defense.
巨噬细胞移动抑制因子（MIF）已成为先天免疫的关键介质，并且已被证明是严重败血症的重要效应分子。类鼻疽是由类鼻疽伯克霍尔德菌引起的，是东南亚社区获得性败血症的重要原因。我们旨在描述 MIF 在类鼻疽中的表达和功能。
从 34 名类鼻疽患者和 32 名对照者的白细胞和血浆中以及感染类鼻疽伯克霍尔德菌的小鼠中确定了 MIF 的表达。使用抗 MIF 抗体和重组 MIF 研究了实验性类鼻疽中的 MIF 功能。患者的白细胞和血浆 MIF mRNA 浓度以及 MIF 浓度明显升高。升高的 MIF 浓度与死亡率相关。用类鼻疽伯克霍尔德菌鼻内接种的小鼠显示肺部和全身 MIF 表达明显增加。感染低接种量时，用抗 MIF 治疗的小鼠肺部的细菌负荷降低。相反，用重组 MIF 治疗的小鼠对类鼻疽伯克霍尔德菌的清除能力略有受损。MIF 对细菌生长或吞噬类鼻疽伯克霍尔德菌没有直接影响。
在临床类鼻疽期间，MIF 浓度明显升高，并与患者的预后相关。在实验性类鼻疽中，MIF 损害了抗菌防御。
