Post-Exposure Therapeutic Efficacy of COX-2 Inhibition against Burkholderia pseudomallei

被引：24

作者：

Asakrah, Saja ^{[1
]}

Nieves, Wildaliz ^{[1
]}

Mahdi, Zaid ^{[1
]}

Agard, Mallory ^{[1
]}

Zea, Arnold H. ^{[2
]}

Roy, Chad J. ^{[3
]}

Morici, Lisa A. ^{[1
]}

机构：

[1] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA

[2] Louisiana State Univ, Hlth Sci Ctr, Sect Pulm & Crit Care Med, New Orleans, LA USA

[3] Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA USA

来源：

PLOS NEGLECTED TROPICAL DISEASES | 2013年 / 7卷 / 05期

基金：

美国国家卫生研究院;

关键词：

III SECRETION SYSTEM; PROSTAGLANDIN E-2; PSEUDOMONAS-AERUGINOSA; MELIOIDOSIS; CELLS; THAILANDENSIS; MODULATION; INFECTION; MACROPHAGES; PROTECTION;

D O I：

10.1371/journal.pntd.0002212

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Burkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in Southeast Asia and Northern Australia. Like other multidrug-resistant pathogens, the inherent antibiotic resistance of B. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. In this work, we demonstrate that host prostaglandin E2 (PGE(2)) production plays a regulatory role in the pathogenesis of B. pseudomallei. PGE(2) promotes B. pseudomallei intracellular survival within macrophages and bacterial virulence in a mouse model of pneumonic melioidosis. PGE(2)-mediated immunosuppression of macrophage bactericidal effector functions is associated with increased arginase 2 (Arg2) expression and decreased nitric oxide (NO) production. Treatment with a commercially-available COX-2 inhibitor suppresses the growth of B. pseudomallei in macrophages and affords significant protection against rapidly lethal pneumonic melioidosis when administered post-exposure to B. pseudomallei-infected mice. COX-2 inhibition may represent a novel immunotherapeutic strategy to control infection with B. pseudomallei and other intracellular pathogens.

引用

页数：10