Escobar Natalia, Ordonez Soledad R, Wösten Han A B, Haas Pieter-Jan A, de Cock Hans, Haagsman Henk P
Department of Microbiology, Institute of Biomembranes, Utrecht University Utrecht, Netherlands.
Department of Infectious Diseases and Immunology, Division Molecular Host Defence, Utrecht University Utrecht, Netherlands.
Front Microbiol. 2016 Apr 6;7:438. doi: 10.3389/fmicb.2016.00438. eCollection 2016.
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.
曲霉属的代表是机会性真菌病原体。它们的分生孢子可通过吸入到达肺泡,并可在免疫功能低下的个体中引发感染。在近90%的病例中,烟曲霉是侵袭性曲霉病的病原体。目前尚不清楚是什么使得这种真菌比其他曲霉(如黑曲霉)更具致病性。在这里,我们表明烟曲霉和黑曲霉的分生孢子以相似的效率粘附于肺上皮A549细胞,但烟曲霉的分生孢子内化效率高17%。两种曲霉的分生孢子在攻击后8小时被吞噬溶酶体摄取。这些细胞器仅在黑曲霉的情况下酸化,这可能是由于分生孢子的黑色素涂层类型所致。两种类型的分生孢子在被吞噬溶酶体摄取后活力均未受到影响。与培养基中的分生孢子相比,上皮细胞存在时烟曲霉和黑曲霉分生孢子的萌发延迟。然而,暴露于A549细胞10小时后,黑曲霉分生孢子的萌发率仍高于烟曲霉。值得注意的是,烟曲霉的菌丝主要平行于上皮生长,而黑曲霉的菌丝生长方向主要垂直于细胞平面。在上皮细胞存在的情况下,中性粒细胞可降低黑曲霉的萌发和菌丝生长,但对烟曲霉没有影响。综上所述,高效内化、萌发延迟以及菌丝平行于上皮生长,为烟曲霉作为肺部机会性病原体比黑曲霉更成功的原因提供了新的见解。