Modeling the catarrhal stage of Bordetella pertussis upper respiratory tract infections in mice.

Modeling the catarrhal stage of Bordetella pertussis upper respiratory tract infections in mice.
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模拟小鼠百日咳博德特氏菌上呼吸道感染的卡他期。

DOI:
10.1242/dmm.049266
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发表时间:
2022-05-01
影响因子:
4.3
通讯作者:
Harvill ET
Harvill ET
中科院分区:
医学2区
文献类型:
--
作者:
Soumana IH;Dewan KK;Linz B;Rivera I;Ma L;Howard LK;Caulfield AD;Sedney CJ;Blas-Machado U;Sebo P;Harvill ET

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百日咳(百日咳)是一种高度传播的人类呼吸道疾病,由百日咳博德特氏菌(一种人类限制性病原体)引起。动物模型通常涉及通过在小鼠肺中沉积大量细菌而诱导的肺炎感染。这些模型告诉我们百日咳的分子发病机制,并指导疫苗的开发,成功地防止严重的疾病。然而,它们绕过了疾病的卡他性阶段,当细菌首先在上呼吸道定植并最初生长时。这是目前疫苗无法预防的感染的关键和高度传播阶段。在这里,我们展示了一个模型系统,其中B。百日咳强烈和持续地感染TLR4缺陷小鼠的鼻咽,诱导局部炎症、嗜中性粒细胞募集和粘液产生以及持续脱落和偶尔传播给笼中的同伴。这种新的实验系统将允许研究细菌因素对鼻咽定植和脱落的贡献,如在百日咳的卡他阶段发生的,以及可能更好地控制百日咳持续循环的干预措施。总结:百日咳的高感染性卡他阶段的小鼠模型,其限制百日咳杆菌感染至上呼吸道,并表现出鼻咽炎症和高水平的脱落。
Pertussis (whooping cough) is a highly transmissible human respiratory disease caused by Bordetella pertussis, a human-restricted pathogen. Animal models generally involve pneumonic infections induced by depositing large numbers of bacteria in the lungs of mice. These models have informed us about the molecular pathogenesis of pertussis and guided development of vaccines that successfully protect against severe disease. However, they bypass the catarrhal stage of the disease, when bacteria first colonize and initially grow in the upper respiratory tract. This is a critical and highly transmissible stage of the infection that current vaccines do not prevent. Here, we demonstrate a model system in which B. pertussis robustly and persistently infects the nasopharynx of TLR4-deficient mice, inducing localized inflammation, neutrophil recruitment and mucus production as well as persistent shedding and occasional transmission to cage mates. This novel experimental system will allow the study of the contributions of bacterial factors to colonization of and shedding from the nasopharynx, as occurs during the catarrhal stage of pertussis, and interventions that might better control the ongoing circulation of pertussis. Summary: Mouse model of the highly infectious catarrhal stage of pertussis that restricts Bordetella pertussis infection to the upper respiratory tract and exhibits nasopharyngeal inflammation and high levels of shedding.
DOI: 10.7554/elife.65663
发表时间: 2021-06-07
期刊: eLife
影响因子: 7.7
作者:
Gill CJ;Gunning CE;MacLeod WB;Mwananyanda L;Thea DM;Pieciak RC;Kwenda G;Mupila Z;Rohani P
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DOI: 10.3389/fendo.2013.00129
发表时间: 2013-09-18
影响因子: 5.2
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Adler KB;Tuvim MJ;Dickey BF
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DOI: 10.3389/fimmu.2014.00461
发表时间: 2014
影响因子: 7.3
作者:
Kawasaki T;Kawai T
通讯作者: Kawai T
DOI: 10.1128/iai.67.11.6109-6118.1999
发表时间: 1999-11-01
影响因子: 3.1
作者:
Harvill, ET;Cotter, PA;Miller, JF
通讯作者: Miller, JF
DOI: 10.1371/journal.ppat.1010402
发表时间: 2022-04
期刊: PLoS pathogens
影响因子: 6.7
作者:
通讯作者: --