Staphylococcus aureus Biofilms Prevent Macrophage Phagocytosis and Attenuate Inflammation In Vivo
Staphylococcus aureus Biofilms Prevent Macrophage Phagocytosis and Attenuate Inflammation In Vivo
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DOI：
10.4049/jimmunol.1002794
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发表时间：
2011-06-01
影响因子：
4.4
通讯作者：
Kielian, Tammy
中科院分区：
文献类型：
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作者：
Thurlow, Lance R.;Hanke, Mark L.;Kielian, Tammy
生物膜是包裹在主要由多糖、胞外DNA和蛋白质组成的基质中的复杂细菌群落。金黄色葡萄球菌可形成生物被膜感染，由于其慢性化和对抗生素治疗的顽固性，通常会使人虚弱。目前，生物膜生长过程中诱导的免疫机制及其对细菌清除的影响仍有待确定。我们使用了导管相关生物膜感染的小鼠模型来评估TLR2和TLR9在生物膜形成期间宿主免疫反应中的功能重要性，因为这两种受体的配体都存在于生物膜中。有趣的是，TLR2和TLR9都没有影响体内生物膜生长过程中的细菌密度或炎症介质的分泌，这表明金黄色葡萄球菌生物膜绕过了这些传统的细菌识别途径。几种可能的机制被认为是生物膜逃避天然免疫的原因，包括与无菌导管引起的伤口愈合反应相比，生物膜感染期间IL-1β、TNF-α、CXCL2和CCL2的表达显著减少，体内巨噬细胞对生物膜的有限入侵，以及免疫反应偏离杀菌表型，这一点从可诱导的一氧化氮合酶表达减少和强烈的精氨酸酶-1诱导相伴随而得到证明。巨噬细胞与金黄色葡萄球菌生物膜的体外共培养研究表明，成功侵入生物膜的巨噬细胞表现出有限的吞噬能力和基因表达模式，这让人想起交替激活的M2巨噬细胞。总而言之，这些发现表明金黄色葡萄球菌生物膜能够减弱传统的宿主前炎症反应，这可能解释了为什么生物膜感染持续存在于具有免疫能力的宿主中。免疫学杂志，2011,186：6585-6596。
Biofilms are complex communities of bacteria encased in a matrix composed primarily of polysaccharides, extracellular DNA, and protein. Staphylococcus aureus can form biofilm infections, which are often debilitating due to their chronicity and recalcitrance to antibiotic therapy. Currently, the immune mechanisms elicited during biofilm growth and their impact on bacterial clearance remain to be defined. We used a mouse model of catheter-associated biofilm infection to assess the functional importance of TLR2 and TLR9 in the host immune response during biofilm formation, because ligands for both receptors are present within the biofilm. Interestingly, neither TLR2 nor TLR9 impacted bacterial density or inflammatory mediator secretion during biofilm growth in vivo, suggesting that S. aureus biofilms circumvent these traditional bacterial recognition pathways. Several potential mechanisms were identified to account for biofilm evasion of innate immunity, including significant reductions in IL-1 beta, TNF-alpha, CXCL2, and CCL2 expression during biofilm infection compared with the wound healing response elicited by sterile catheters, limited macrophage invasion into biofilms in vivo, and a skewing of the immune response away from a microbicidal phenotype as evidenced by decreases in inducible NO synthase expression concomitant with robust arginase-1 induction. Coculture studies of macrophages with S. aureus biofilms in vitro revealed that macrophages successful at biofilm invasion displayed limited phagocytosis and gene expression patterns reminiscent of alternatively activated M2 macrophages. Collectively, these findings demonstrate that S. aureus biofilms are capable of attenuating traditional host proinflammatory responses, which may explain why biofilm infections persist in an immunocompetent host. The Journal of Immunology, 2011, 186: 6585-6596.