Lipooligosaccharides containing phosphorylcholine delay pulmonary clearance of nontypeable Haemophilus influenzae
Lipooligosaccharides containing phosphorylcholine delay pulmonary clearance of nontypeable Haemophilus influenzae
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DOI：
10.1128/iai.01716-07
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发表时间：
2008-05-01
影响因子：
3.1
通讯作者：
Swords, W. Edward
中科院分区：
文献类型：
--
作者：
Pang, Bing;Winn, Dana;Swords, W. Edward
无法分型的流感嗜血杆菌（NTHi）可导致慢性阻塞性肺病和其他粘液纤毛清除缺陷患者的肺部感染。像许多栖息在粘膜表面的细菌一样，NTHi产生缺乏O侧链的脂寡糖（LOS）内毒素。持续性NTHi群体表达LOS糖型的离散子集，包括含有磷酸胆碱（PCo）的那些。在这项研究中，我们比较了两个NTHi菌株与同基因突变体缺乏PCo清除小鼠肺部感染。与其他模型系统的数据一致，从小鼠肺中回收的菌株NTHi 2019和NTHi 86- 028 NP的群体中含有的PCho（+）变体比例高于接种物中的比例。PCo（-）突变体被更快地清除。连续传代的NTHi增加了PCo含量和细菌对清除的抗性，而PCo（-）突变体没有观察到这种增加。在非内毒素应答的C3 H/HeJ和Toll样受体4缺失（TLR 4（-/-））小鼠的NTHi群体中也观察到PCo含量增加，尽管是在感染后较晚的时间。与亲代菌株小鼠中的亚群和清除率相比，TLR 2（-/-）小鼠中细菌亚群和清除率的变化未受影响。在两种品系背景和所有类型的小鼠中，PCo（-）突变体的清除发生在较早的时间点。通过免疫荧光染色比较肺组织冷冻切片中的细菌种群显示，C57 BL/6小鼠的空气空间内有稀疏的细菌，MyD 88（-/-）小鼠的肺内有大的细菌聚集体。这些结果表明，PCho在感染早期以至少部分独立于TLR 4途径的方式促进细菌对肺清除的抗性。
Nontypeable Haemophilus influenzae (NTHi) causes pulmonary infections in patients with chronic obstructive pulmonary disease and other mucociliary clearance defects. Like many bacteria inhabiting mucosal surfaces, NTHi produces lipooligosaccharide (LOS) endotoxins that lack the O side chain. Persistent NTHi populations express a discrete subset of LOS glycoforms, including those containing phosphorylcholine (PCho). In this study, we compared two NTHi strains with isogenic mutants lacking PCho for clearance from mice following pulmonary infection. Consistent with data from other model systems, populations of the strains NTHi 2019 and NTHi 86-028NP recovered from mouse lung contained an increased proportion of PCho(+) variants compared to that in the inocula. PCho(-) mutants were more rapidly cleared. Serial passage of NTHi increased both PCho content and bacterial resistance to clearance, and no such increases were observed for PCho(-) mutants. Increased PCho content was also observed in NTHi populations within non-endotoxin-responsive C3H/HeJ and Toll-like receptor 4 null (TLR4(-/-)) mice, albeit at later times postinfection. Changes in bacterial subpopulations and clearance were unaffected in TLR2(-/-) mice compared to the subpopulations in and clearance from mice of the parental strain. The clearance of PCho(-) mutants occurred at earlier time points in both strain backgrounds and in all types of mice. Comparison of bacterial populations in lung tissue cryosections by immunofluorescent staining showed sparse bacteria within the air spaces of C57BL/6 mice and large bacterial aggregates within the lungs of MyD88(-/-) mice. These results indicate that PCho promotes bacterial resistance to pulmonary clearance early in infection in a manner that is at least partially independent of the TLR4 pathway.