Hide, Keep Quiet, and Keep Low: Properties That Make Aspergillus fumigatus a Successful Lung Pathogen.
Hide, Keep Quiet, and Keep Low: Properties That Make Aspergillus fumigatus a Successful Lung Pathogen.
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DOI：
10.3389/fmicb.2016.00438
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发表时间：
2016
影响因子：
5.2
通讯作者：
Haagsman HP
中科院分区：
文献类型：
--
作者：
Escobar N;Ordonez SR;Wösten HA;Haas PJ;de Cock H;Haagsman HP
曲霉属的代表是机会性真菌病原体。它们的分生孢子可以通过吸入到达肺泡，并可能引起免疫功能低下个体的感染。烟曲霉是近 90% 病例中侵袭性曲霉病的病原体。目前尚不清楚是什么使这种真菌比其他曲霉（例如黑曲霉）更具致病性。在这里，我们发现烟曲霉和黑曲霉分生孢子对肺上皮 A549 细胞的粘附效率相似，但烟曲霉分生孢子内化的效率高出 17%。攻击后8小时，两种曲霉的分生孢子均被吞噬溶酶体吸收。这些细胞器仅在黑曲霉的情况下被酸化，这可能是由于分生孢子的黑色素涂层类型所致。两种类型分生孢子的活力在被吞噬溶酶体摄取后均不受影响。与培养基中的分生孢子相比，烟曲霉和黑曲霉分生孢子在上皮细胞存在下的萌发被延迟。然而，接触A549细胞10小时后，黑曲霉分生孢子的萌发率仍然高于烟曲霉。值得注意的是，烟曲霉菌丝主要平行于上皮生长，而黑曲霉菌丝的生长方向主要垂直于细胞平面。在上皮细胞存在的情况下，中性粒细胞会减少黑曲霉的发芽和菌丝生长，但不会减少烟曲霉的发芽和菌丝生长。总而言之，高效的内化、延迟的发芽以及与上皮平行的菌丝生长，为烟曲霉与黑曲霉作为肺部机会性病原体的成功原因提供了新的见解。
Representatives of the genus Aspergillus are opportunistic fungal pathogens. Their conidia can reach the alveoli by inhalation and can give rise to infections in immunocompromised individuals. Aspergillus fumigatus is the causal agent of invasive aspergillosis in nearly 90% of the cases. It is not yet well-established what makes this fungus more pathogenic than other aspergilli such as A. niger. Here, we show that A. fumigatus and A. niger conidia adhere with similar efficiency to lung epithelial A549 cells but A. fumigatus conidia internalized 17% more efficiently. Conidia of both aspergilli were taken up in phagolysosomes 8 h after the challenge. These organelles only acidified in the case of A. niger, which is probably due to the type of melanin coating of the conidia. Viability of both types of conidia was not affected after uptake in the phagolysosomes. Germination of A. fumigatus and A. niger conidia in the presence of epithelial cells was delayed when compared to conidia in the medium. However, germination of A. niger conidia was still higher than that of A. fumigatus 10 h after exposure to A549 cells. Remarkably, A. fumigatus hyphae grew mainly parallel to the epithelium, while growth direction of A. niger hyphae was predominantly perpendicular to the plane of the cells. Neutrophils reduced germination and hyphal growth of A. niger, but not of A fumigatus, in presence of epithelial cells. Taken together, efficient internalization, delayed germination, and hyphal growth parallel to the epithelium gives a new insight into what could be the causes for the success of A. fumigatus compared to A. niger as an opportunistic pathogen in the lung.