A new model for non-typeable Haemophilus influenzae middle ear infection in the Junbo mutant mouse.
A new model for non-typeable Haemophilus influenzae middle ear infection in the Junbo mutant mouse.
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DOI：
10.1242/dmm.021659
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发表时间：
2016-01
影响因子：
4.3
通讯作者：
Cheeseman MT
中科院分区：
文献类型：
--
作者：
Hood D;Moxon R;Purnell T;Richter C;Williams D;Azar A;Crompton M;Wells S;Fray M;Brown SD;Cheeseman MT
急性中耳炎，中耳炎，是儿童中最常见的细菌感染，因此，是该年龄组抗生素处方的最常见原因。目前还没有针对所涉及的主要病原体，即不可分型流感嗜血杆菌（NTHi）的有效疫苗。最常用和广泛接受的中耳感染实验动物模型是龙猫，但小鼠和沙鼠也被使用。我们已经在Junbo小鼠中建立了NTHi中耳感染的稳健模型，Junbo小鼠是一种突变小鼠系，其在特定的无病原体条件下自发发展慢性中耳炎症。杂合子Junbo小鼠（Jbo/+）携带在宿主先天免疫调节中起作用的基因（Evi 1，也称为Mecom）突变;预先存在的中耳炎症促进NTHi中耳感染。单次鼻内接种NTHi可产生高比率（高达90%）的中耳感染和大疱液中的细菌滴度（104-105菌落形成单位/μl）。细菌在接种后第21天至第35天从大多数中耳中清除，但在感染后至少56天仍保留在约20%的中耳中。NTHi感染后Jbo/+小鼠中耳中Toll样受体依赖性应答细胞因子基因的表达升高。Junbo模型用于研究抗微生物干预方案的转化潜力显示为使用阿奇霉素的3天疗程来清除NTHi感染，并且其在疫苗开发研究中的潜在用途通过证明在用杀死的同源而非异源NTHi细菌免疫的小鼠中的保护来显示。 急性中耳炎是儿童的一种重要疾病。我们描述了一种新的感染模型的转化研究，使用Junbo小鼠突变体鼻内接种不可分型流感嗜血杆菌。
Acute otitis media, inflammation of the middle ear, is the most common bacterial infection in children and, as a consequence, is the most common reason for antimicrobial prescription to this age group. There is currently no effective vaccine for the principal pathogen involved, non-typeable Haemophilus influenzae (NTHi). The most frequently used and widely accepted experimental animal model of middle ear infection is in chinchillas, but mice and gerbils have also been used. We have established a robust model of middle ear infection by NTHi in the Junbo mouse, a mutant mouse line that spontaneously develops chronic middle ear inflammation in specific pathogen-free conditions. The heterozygote Junbo mouse (Jbo/+) bears a mutation in a gene (Evi1, also known as Mecom) that plays a role in host innate immune regulation; pre-existing middle ear inflammation promotes NTHi middle ear infection. A single intranasal inoculation with NTHi produces high rates (up to 90%) of middle ear infection and bacterial titres (104-105 colony-forming units/µl) in bulla fluids. Bacteria are cleared from the majority of middle ears between day 21 and 35 post-inoculation but remain in approximately 20% of middle ears at least up to day 56 post-infection. The expression of Toll-like receptor-dependent response cytokine genes is elevated in the middle ear of the Jbo/+ mouse following NTHi infection. The translational potential of the Junbo model for studying antimicrobial intervention regimens was shown using a 3 day course of azithromycin to clear NTHi infection, and its potential use in vaccine development studies was shown by demonstrating protection in mice immunized with killed homologous, but not heterologous, NTHi bacteria. Summary: Acute otitis media is an important disease in children. We describe a new infection model for translational research that uses the Junbo mouse mutant intranasally inoculated with non-typeable Haemophilus influenzae.