Féménia F, Huet D, Lair-Fulleringer S, Wagner M C, Sarfati J, Shingarova L, Guillot J, Boireau P, Chermette R, Berkova N
INRA, AFSSA, ENVA, UMR 956; 22 rue Curie, 94700, Maisons Alfort Cedex, France.
Mycopathologia. 2009 May;167(5):249-62. doi: 10.1007/s11046-008-9175-3. Epub 2009 Jan 1.
Aspergillus species can cause mycoses in human and animals. Previously, we demonstrated that A. fumigatus conidia from a human isolate inhibited apoptosis in human pneumocytes and bronchial epithelial cells. In the current study, we studied the effects of A. fumigatus conidia non-human origin and A. flavus, A. nidulans, A. niger and A. oryzae conidia on human cells apoptosis. Human pneumocytes or bronchial epithelial cells were simultaneously exposed to apoptotic inductors and aspergilli conidia. The cell cultures were analyzed by flow cytometry, immunoblotting, and examination of nuclear morphology. Similar to A. fumigatus conidia, A. flavus conidia inhibited cellular apoptosis while A. nidulans, A. niger and A. oryzae conidia did not affect apoptosis. We further studied the species specificity of conidia: there were no differences in the inhibition of apoptosis by A. fumigatus conidia from either human or bird isolates. In order to determine whether the inhibition of apoptosis by conidia is limited to certain strains, the effect on human cell apoptosis of different A. fumigatus human clinical isolates and A. fumigatus of environmental origin was evaluated. All A. fumigatus isolates inhibited apoptosis; an anti-apoptotic factor was released by conidia. For TNF-induced apoptosis, the anti-apoptotic effect of conidia of all isolates was found to be associated with a reduction of caspase-3 in human cells. The results suggest that suppression of apoptosis may play a role in reducing the efficacy of host defense mechanisms during infection with Aspergillus species.
曲霉菌可在人类和动物中引起真菌病。此前,我们证明来自人类分离株的烟曲霉分生孢子可抑制人肺细胞和支气管上皮细胞的凋亡。在本研究中,我们研究了非人类来源的烟曲霉分生孢子以及黄曲霉、构巢曲霉、黑曲霉和米曲霉分生孢子对人细胞凋亡的影响。将人肺细胞或支气管上皮细胞同时暴露于凋亡诱导剂和曲霉菌分生孢子中。通过流式细胞术、免疫印迹和核形态学检查对细胞培养物进行分析。与烟曲霉分生孢子相似,黄曲霉分生孢子可抑制细胞凋亡,而构巢曲霉、黑曲霉和米曲霉分生孢子不影响凋亡。我们进一步研究了分生孢子的种属特异性:来自人类或鸟类分离株的烟曲霉分生孢子对凋亡的抑制作用没有差异。为了确定分生孢子对凋亡的抑制是否仅限于某些菌株,评估了不同的烟曲霉临床分离株和环境来源的烟曲霉对人细胞凋亡的影响。所有烟曲霉分离株均抑制凋亡;分生孢子释放出一种抗凋亡因子。对于肿瘤坏死因子诱导的凋亡,发现所有分离株的分生孢子的抗凋亡作用与人细胞中半胱天冬酶-3的减少有关。结果表明,凋亡抑制可能在曲霉菌感染期间宿主防御机制效能降低中起作用。