期刊
JOURNAL OF IMMUNOLOGY
卷 190, 期 5, 页码 2159-2168出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1202348
关键词
-
类别
资金
- National Institutes of Health National Institute of Allergy and Infectious Disease [P01 AI083211]
Biofilm infections often lead to significant morbidity due to their chronicity and recalcitrance to antibiotics. We have demonstrated that methicillin-resistant Staphylococcus aureus (MRSA) biofilms can evade macrophage (M Phi) antibacterial effector mechanisms by skewing M Phi s toward an alternatively activated M2 phenotype. To overcome this immune evasion, we have used two complementary approaches. In the first, a proinflammatory milieu was elicited by local administration of classically activated M1 M Phi s and in the second by treatment with the C5a receptor (CD88) agonist EP67, which invokes M Phi proinflammatory activity. Early administration of M1-activated M Phi s or EP67 significantly attenuated biofilm formation in a mouse model of MRSA catheter-associated infection. Several proinflammatory mediators were significantly elevated in biofilm-infected tissues from M Phi- and EP67-treated animals, revealing effective reprogramming of the biofilm environment to a proinflammatory milieu. A requirement for M Phi proinflammatory activity was demonstrated by the fact that transfer of MyD88-deficient M Phi s had minimal impact on biofilm growth. Likewise, neutrophil administration had no effect on biofilm formation. Treatment of established biofilm infections with M1-activated M Phi s also significantly reduced catheter-associated biofilm burdens compared with antibiotic treatment. Collectively, these results demonstrate that targeting M Phi proinflammatory activity can overcome the local immune inhibitory environment created during biofilm infections and represents a novel therapeutic strategy. The Journal of Immunology, 2013, 190: 2159-2168.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据