Virulence of Mycobacterium intracellulare clinical strains in a mouse model of lung infection - role of neutrophilic inflammation in disease severity.

Virulence of Mycobacterium intracellulare clinical strains in a mouse model of lung infection - role of neutrophilic inflammation in disease severity.
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DOI:
10.1186/s12866-023-02831-y
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发表时间:
2023-04-03
期刊:
影响因子:
4.2
通讯作者:
Matsumoto, Sohkichi
Matsumoto, Sohkichi
中科院分区:
生物学3区
文献类型:
--
作者:
Tateishi, Yoshitaka;Ozeki, Yuriko;Nishiyama, Akihito;Miki, Mari;Maekura, Ryoji;Kida, Hiroshi;Matsumoto, Sohkichi

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胞内分枝杆菌是鸟胞内分枝杆菌肺病(MAC-PD)的主要病原体。然而,M.细胞内和体内化疗功效仍然不清楚。在这项研究中,我们检查了9个M. C57 BL/6小鼠中具有不同临床表型和基因型的细胞内菌株。我们根据细菌载量、组织学肺部炎症和嗜酸性粒细胞浸润的动力学将毒力表型分为三种类型(高、中和低)。高毒力株肺内嗜中性粒细胞浸润较中、低毒力株严重,支气管肺泡灌洗液中性粒细胞平均百分比分别为中、低毒力株的6.27倍和11.0倍。特别是,高毒力菌株M.i.198在小鼠中显示出最高的死亡率,这与临床疾病的快速进展相对应。在感染药物敏感的高毒力菌株M019的小鼠中,含克拉霉素的化疗显示出最高的疗效。利福平单药治疗加重了肺部炎症,淋巴细胞和嗜中性粒细胞浸润增加。临床分离株的毒力表型。细胞内菌株多种多样,高毒力菌株与感染小鼠的中性粒细胞浸润和疾病进展相关。这些高毒力菌株被提议作为体内化疗实验的有用对象。在线版本包含补充材料,可通过10.1186/s12866-023-02831-y获得。
Mycobacterium intracellulare is a major etiological agent of Mycobacterium avium-intracellulare pulmonary disease (MAC-PD). However, the characteristics of the virulence of M. intracellulare and the in vivo chemotherapeutic efficacy remain unclear. In this study, we examined the virulence of nine M. intracellulare strains with different clinical phenotypes and genotypes in C57BL/6 mice. We classified three types of virulence phenotypes (high, intermediate, and low) based on the kinetics of the bacterial load, histological lung inflammation, and neutrophilic infiltration. High virulence strains showed more severe neutrophilic infiltration in the lungs than intermediate and low virulence strains, with 6.27-fold and 11.0-fold differences of the average percentage of neutrophils in bronchoalveolar lavage fluid, respectively. In particular, the high virulence strain M.i.198 showed the highest mortality in mice, which corresponded to the rapid progression of clinical disease. In mice infected with the drug-sensitive high virulence strain M019, clarithromycin-containing chemotherapy showed the highest efficacy. Monotherapy with rifampicin exacerbated lung inflammation with increased lymphocytic and neutrophilic infiltration into the lungs. The virulence phenotypes of clinical strains of M. intracellulare were diverse, with high virulence strains being associated with neutrophilic infiltration and disease progression in infected mice. These high virulence strains were proposed as a useful subject for in vivo chemotherapeutic experiments. The online version contains supplementary material available at 10.1186/s12866-023-02831-y.
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