Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice.
Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice.
复制标题
烟曲霉预暴露会恶化小鼠的病理学并改善对脓肿分枝杆菌肺部感染的控制。
DOI：
10.1128/iai.00859-17
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发表时间：
2018
影响因子：
3.1
通讯作者：
Khader,ShabaanaA
中科院分区：
文献类型：
--
作者：
Monin,Leticia;Mehta,Shail;Elsegeiny,Waleed;Gopal,Radha;McAleer,JeremyP;Oury,TimD;Kolls,Jay;Khader,ShabaanaA
囊性纤维化是一种常染色体隐性遗传病，由囊性纤维化跨膜电导调节基因突变引起。这种氯离子通道的突变会导致粘液堆积，随后反复发生肺部感染和炎症，进而导致慢性肺部疾病和呼吸衰竭。近年来，CF患者中非结核分枝杆菌(NTM)感染率呈上升趋势。尤其相关的是感染脓肿分枝杆菌，这会导致一种严重的危及生命的疾病，并构成对抗生素抗药性最强的非传染性疾病之一。有趣的是，在同时感染烟曲霉菌的CF患者中，NTM感染的增加与肺功能恶化有关。我们建立了一种新的小鼠模型来研究烟曲霉菌与脓肿支原体肺部感染的关系。在这个模型中，与单独感染脓肿分支杆菌的小鼠相比，暴露于烟曲霉菌并合并感染脓肿分支杆菌的动物表现出更高的肺部炎症和更低的分枝杆菌负荷。这种对混合感染小鼠脓肿支原体感染的增强控制不依赖于粘液，但依赖于转录因子T-box21(Tbx21)和维甲酸受体相关孤儿受体γt(RoRγ-t)，它们分别是1型和17型免疫反应的主要调节因子。这些结果暗示了1型和17型反应在感染烟曲霉菌的肺部脓肿分枝杆菌控制中的作用。我们的结果表明，烟曲霉菌是一种在患有NTM感染的CF患者中常见的微生物，在小鼠模型中可以加重肺部炎症并影响对脓肿的控制。
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with Mycobacterium abscessus, which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with Aspergillus fumigatus. We established a new mouse model to investigate the relationship between A. fumigatus and M. abscessus pulmonary infections. In this model, animals exposed to A. fumigatus and coinfected with M. abscessus exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with M. abscessus alone. This increased control of M. abscessus infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in M. abscessus control in A. fumigatus-coinfected lungs. Our results demonstrate that A. fumigatus, an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact M. abscessus control in a mouse model.