Inducible expression of beta defensins by human respiratory epithelial cells exposed to Aspergillus fumigatus organisms.
Inducible expression of beta defensins by human respiratory epithelial cells exposed to Aspergillus fumigatus organisms.
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DOI：
10.1186/1471-2180-9-33
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发表时间：
2009-02-11
期刊：
影响因子：
4.2
通讯作者：
Berkova N
中科院分区：
文献类型：
--
作者：
Alekseeva L;Huet D;Féménia F;Mouyna I;Abdelouahab M;Cagna A;Guerrier D;Tichanné-Seltzer V;Baeza-Squiban A;Chermette R;Latgé JP;Berkova N
烟曲霉菌是一种致病霉菌，可引起免疫功能低下宿主发生危及生命的侵袭性肺部疾病。气道上皮的作用涉及与吸入的病原体的复杂相互作用。具有直接抗真菌和趋化活性的抗菌肽可能会增强抗真菌免疫应答。A.人支气管上皮细胞16 HBE和肺上皮细胞A549在A.烟曲霉进行了调查。使用RT-PCR和真实的时间PCR，我们显示了hBD 2和hBD 9防御素基因的激活：在细胞暴露于肿胀的分生孢子（SC），比静止的分生孢子（RC）或菌丝片段（HF）的表达更高。防御素表达的动力学是不同的每一个，唤起一个假定的不同功能，每个研究防御素。在热灭活血清的存在下，防御素表达的减少表明防御素和宿主补体系统的蛋白质之间可能存在联系。使用免疫荧光显示点状细胞质和核周染色，揭示了防御素肽hBD 2的存在。用抗hBD 2抗体染色的细胞的定量表明，与RC或HF相比，SC诱导更多数量的合成hBD 2的细胞。用抗hBD-2抗体标记的细胞在RC或SC周围显示阳性免疫荧光信号，与HF相反。这表明hBD 2和消化的分生孢子的共定位。HBD 2水平在暴露于SC的细胞的上清液中最高，如通过夹心ELISA测定的。利用中和抗白细胞介素-1 β抗体的实验反映了SC诱导防御素表达的自分泌机制。在转录和转录后水平上对防御素表达的研究表明，在A.烟曲霉防御素诱导最后，在原代培养的人呼吸道细胞中，A. fumigatus指出了所述现象的生物学意义。我们的研究结果提供了证据表明呼吸道上皮可能在曲霉菌感染期间的免疫反应中发挥重要作用。了解防御素表达的调节机制，从而可能导致新的方法，可以提高抗微生物肽的表达，在曲霉病治疗的潜在治疗用途。
Aspergillus fumigatus, a saprophytic mould, is responsible for life-threatening, invasive pulmonary diseases in immunocompromised hosts. The role of the airway epithelium involves a complex interaction with the inhaled pathogen. Antimicrobial peptides with direct antifungal and chemotactic activities may boost antifungal immune response. The inducible expression of defensins by human bronchial epithelial 16HBE cells and A549 pneumocyte cells exposed to A. fumigatus was investigated. Using RT-PCR and real time PCR, we showed an activation of hBD2 and hBD9 defensin genes: the expression was higher in cells exposed to swollen conidia (SC), compared to resting conidia (RC) or hyphal fragments (HF). The kinetics of defensin expression was different for each one, evoking a putative distinct function for each investigated defensin. The decrease of defensin expression in the presence of heat-inactivated serum indicated a possible link between defensins and the proteins of the host complement system. The presence of defensin peptide hBD2 was revealed using immunofluorescence that showed a punctual cytoplasmic and perinuclear staining. Quantification of the cells stained with anti hBD2 antibody demonstrated that SC induced a greater number of cells that synthesized hBD2, compared to RC or HF. Labelling of the cells with anti-hBD-2 antibody showed a positive immunofluorescence signal around RC or SC in contrast to HF. This suggests co-localisation of hBD2 and digested conidia. The HBD2 level was highest in the supernatants of cells exposed to SC, as was determined by sandwich ELISA. Experiments using neutralising anti-interleukine-1β antibody reflect the autocrine mechanism of defensin expression induced by SC. Investigation of defensin expression at transcriptional and post-transcriptional levels demonstrated the requirement of transcription as well as new protein synthesis during A. fumigatus defensin induction. Finally, induced defensin expression in primary culture of human respiratory cells exposed to A. fumigatus points to the biological significance of described phenomena. Our findings provide evidence that respiratory epithelium might play an important role in the immune response during Aspergillus infection. Understanding the mechanisms of regulation of defensin expression may thus lead to new approaches that could enhance expression of antimicrobial peptides for potential therapeutic use during aspergillosis treatment.
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影响因子：
3.1
作者：
Krisanaprakornkit, S;Kimball, JR;Dale, DA
通讯作者：
Dale, DA
影响因子：
2.9
作者：
Bellocchio, S;Bozza, S;Romani, L
通讯作者：
Romani, L
影响因子：
5.5
作者：
Cunliffe, RN;Mahida, YR
通讯作者：
Mahida, YR
影响因子：
20.3
作者：
Bezerra, LML;Filler, SG
通讯作者：
Filler, SG
影响因子：
3.5
作者：
BENSCH, KW;RAIDA, M;FORSSMANN, WG
通讯作者：
FORSSMANN, WG