Respiratory syncytial virus-induced dysregulation of expression of a mucosal beta-defensin augments colonization of the upper airway by non-typeable Haemophilus influenzae.
Respiratory syncytial virus-induced dysregulation of expression of a mucosal beta-defensin augments colonization of the upper airway by non-typeable Haemophilus influenzae.
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DOI：
10.1111/j.1462-5822.2009.01339.x
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发表时间：
2009-09
影响因子：
3.4
通讯作者：
Bakaletz LO
中科院分区：
文献类型：
--
作者：
McGillivary G;Mason KM;Jurcisek JA;Peeples ME;Bakaletz LO
中耳炎（OM）是一种多微生物疾病，其中上呼吸道（URT）病毒破坏宿主气道防御，使鼻咽部（NP）的细菌菌群进入中耳。我们已经证明，在体外，呼吸道合胞病毒（RSV），一种OM的病毒共病原体，降低抗菌肽（AP），栗鼠β -防御素-1 （cBD-1）的转录丰度。在这里，我们证明了接种RSV的龙猫表达的cBD-1 mRNA和蛋白比模拟攻击的动物少40%。此外，与没有病毒共感染的龙猫相比，并发RSV感染导致从鼻咽灌洗液中恢复非分型流感嗜血杆菌（NTHI）的10-100倍。此外，当将抗cBD-1抗体（结合分泌AP）或重组cBD-1（增加粘膜表面AP浓度）传递给龙猫时，我们证明破坏单一AP的可用性会影响上呼吸道NTHI的相对负荷。总的来说，我们的数据表明，先天免疫效应物调节NP的正常细菌定植，而且，病毒诱导的APs表达改变可能导致NP内NTHI负荷增加，这可能促进OM的发展。
Otitis media (OM) is a polymicrobial disease wherein upper respiratory tract (URT) viruses compromise host airway defenses, which allows bacterial flora of the nasopharynx (NP) access to the middle ear. We have shown, in vitro, that respiratory syncytial virus (RSV), a viral co-pathogen of OM, reduces transcript abundance of the antimicrobial peptide (AP), chinchilla beta-defensin-1 (cBD-1). Here, we demonstrated that chinchillas inoculated with RSV expressed ~40% less cBD-1 mRNA and protein than did mock-challenged animals. Further, concurrent RSV infection resulted in a 10–100 fold greater recovery of nontypeable Haemophilus influenzae (NTHI) from nasopharyngeal lavage fluids, compared to chinchillas challenged with NTHI in the absence of viral co-infection. Additionally, when either: anti-cBD-1 antibody (to bind secreted AP) or recombinant cBD-1 (to increase AP concentration at the mucosal surface) were delivered to chinchillas, we demonstrated that disruption of the availability of a single AP influenced the relative load of NTHI in the URT. Collectively, our data suggested that effectors of innate immunity regulate normal bacterial colonization of the NP, and, further, virus-induced altered expression of APs can result in an increased load of NTHI within the NP which likely promotes development of OM.
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DOI：
10.4049/jimmunol.181.10.6692
发表时间：
2008-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Castilow EM;Legge KL;Varga SM
通讯作者：
Varga SM
影响因子：
5.4
作者：
Gitiban, N;Jurcisek, JA;Durbin, JE
通讯作者：
Durbin, JE
影响因子：
5.4
作者：
Janssen, Riny;Pennings, Jeroen;Hoebee, Barbara
通讯作者：
Hoebee, Barbara
影响因子：
3.1
作者：
Mason, KM;Munson, RS;Bakaletz, LO
通讯作者：
Bakaletz, LO
影响因子：
82.9
作者：
Chromek, Milan;Slamova, Zuzana;Brauner, Annelie
通讯作者：
Brauner, Annelie