Nontypeable Haemophilus influenzae Initiates Formation of Neutrophil Extracellular Traps
Nontypeable Haemophilus influenzae Initiates Formation of Neutrophil Extracellular Traps
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DOI：
10.1128/iai.00660-10
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发表时间：
2011-01-01
影响因子：
3.1
通讯作者：
Swords, W. Edward
中科院分区：
文献类型：
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作者：
Juneau, Richard A.;Pang, Bing;Swords, W. Edward
不可分型流感嗜血杆菌 (NTHI) 是中耳炎感染的主要原因，这种感染通常是慢性和/或复发性的。在中耳炎和其他持续性感染期间，NTHI 和其他细菌种类在体内生物膜内持续存在。这些生物膜具有重要的宿主成分，其中包括中性粒细胞胞外陷阱（NET）。这些 NET 不介导 NTHI 的清除，NTHI 通过细菌表面的脂寡糖的特定亚群在 NET 结构中存活，而细菌表面的脂寡糖亚群是体外生物膜形成的决定因素。在这项研究中，使用体外模型系统检查了 NTHI 和 NTHI 成分启动 NET 形成的能力。活的和非活的 NTHI 菌株都被证明可以促进 NET 的形成，细菌 DNA、外膜蛋白和脂寡糖（内毒素）的制剂也是如此。然而，只有来自 NTHI 亲本菌株的内毒素在 NET 形成方面表现出与 NTHI 相同的效力。其他研究表明，由于脂寡糖内的寡糖部分，包埋在 NET 结构内的 NTHI 可抵抗 NET 内的细胞外杀伤和传入中性粒细胞的吞噬杀伤。因此，我们得出结论，NTHI 通过多种病原体相关分子模式（最显着的是内毒素）引发 NET 形成，并且对 NET 结构内的杀伤具有高度抵抗力。这些数据支持这样的结论：对于 NTHI，NET 结构的形成可能是通过在中耳室内提供一个利基来持久性的决定因素。
Nontypeable Haemophilus influenzae (NTHI) is a leading cause of otitis media infections, which are often chronic and/or recurrent in nature. NTHI and other bacterial species persist in vivo within biofilms during otitis media and other persistent infections. These biofilms have a significant host component that includes neutrophil extracellular traps (NETs). These NETs do not mediate clearance of NTHI, which survives within NET structures by means of specific subpopulations of lipooligosaccharides on the bacterial surface that are determinants of biofilm formation in vitro. In this study, the ability of NTHI and NTHI components to initiate NET formation was examined using an in vitro model system. Both viable and nonviable NTHI strains were shown to promote NET formation, as did preparations of bacterial DNA, outer membrane proteins, and lipooligosaccharide (endotoxin). However, only endotoxin from a parental strain of NTHI exhibited equivalent potency in NET formation to that of NTHI. Additional studies showed that NTHI entrapped within NET structures is resistant to both extracellular killing within NETs and phagocytic killing by incoming neutrophils, due to oligosaccharide moieties within the lipooligosaccharides. Thus, we concluded that NTHI elicits NET formation by means of multiple pathogen-associated molecular patterns (most notably endotoxin) and is highly resistant to killing within NET structures. These data support the conclusion that, for NTHI, formation of NET structures may be a persistence determinant by providing a niche within the middle-ear chamber.