Expression and Function of Macrophage Migration Inhibitory Factor (MIF) in Melioidosis

被引：16

作者：

Wiersinga, W. Joost ^{[1
,2
]}

Calandra, Thierry ^{[3
,4
]}

Kager, Liesbeth M. ^{[1
,2
]}

van der Windt, Gerritje J. W. ^{[1
,2
]}

Roger, Thierry ^{[3
,4
]}

le Roy, Didier ^{[3
,4
]}

Florquin, Sandrine ^{[5
]}

Peacock, Sharon J. ^{[6
,7
]}

Sweep, Fred C. G. J. ^{[8
]}

van der Poll, Tom ^{[1
,2
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, CINIMA, NL-1105 AZ Amsterdam, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, CEMM, NL-1105 AZ Amsterdam, Netherlands

[3] CHU Vaudois, Dept Med, Infect Dis Serv, Lausanne, Switzerland

[4] Univ Lausanne, Lausanne, Switzerland

[5] Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands

[6] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand

[7] Univ Oxford, Nuffield Dept Clin Med, Ctr Clin Vaccinol & Trop Med, Oxford, England

[8] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands

来源：

PLOS NEGLECTED TROPICAL DISEASES | 2010年 / 4卷 / 02期

基金：

瑞士国家科学基金会; 英国惠康基金;

关键词：

INNATE IMMUNE-RESPONSES; TOLL-LIKE RECEPTOR-4; BURKHOLDERIA-PSEUDOMALLEI; SEVERE SEPSIS; PULMONARY TUBERCULOSIS; SEPTIC SHOCK; ACTIVE-SITE; MICE; SERUM; ENDOTOXEMIA;

D O I：

10.1371/journal.pntd.0000605

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Background: 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. Methodology and Principal Findings: 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. Conclusions: MIF concentrations are markedly elevated during clinical melioidosis and correlate with patients' outcomes. In experimental melioidosis MIF impaired antibacterial defense.

引用

页数：8

共 51 条

[1] ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis [J].