Transcriptome Profiles of Human Lung Epithelial Cells A549 Interacting with Aspergillus fumigatus by RNA-Seq

Chen, Fangyan; Zhang, Changjian; Jia, Xiaodong; Wang, Shuo; Wang, Jing; Chen, Yong; Zhao, Jingya; Tian, Shen; Han, Xiaonan; Han, Li

doi:10.1371/journal.pone.0135720

Cited by 46 publications

(62 citation statements)

References 46 publications

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“…Furthermore, acting as an epithelial‐mesenchymal trophic unit, injured airway epithelial cells signal to underlying mesenchymal cells and vice versa . A fumigatus up‐regulates a number of key cytokines in airway epithelial cells . Intriguingly in the present study, we found that both A fumigatus spores and culture filtrate also caused an up‐regulation of ET‐1 in airway epithelial cells, with no significant change detected for TGF‐β1 or periostin and a decrease in TGF‐β2 compared with untreated controls.…”

Section: Discussionsupporting

confidence: 72%

“…Furthermore, signalling through an epithelial‐mesenchymal trophic unit (EMTU) may enable epithelial cells to regulate fibroblast behaviour in the subepithelial layer so governing the extent of repair following airway damage. Previous studies have shown that airway epithelial cells respond to germinating spores and hyphae of A fumigatus via production of a number of key cytokines including IL6, IL8, GM‐CSF and TNF‐α . In addition, we and others have established that inhalation of components of A fumigatus in vivo elicits airway inflammatory and remodelling responses through release of secreted fungal products including allergens with protease activity .…”

Section: Introductionmentioning

confidence: 92%

See 1 more Smart Citation

Endothelin‐1 mediates Aspergillus fumigatus‐induced airway inflammation and remodelling

Labram

Namvar

Hussell

et al. 2019

Clin Experimental Allergy

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Summary Background Asthma is a chronic inflammatory condition of the airways and patients sensitized to airborne fungi such as Aspergillus fumigatus have more severe asthma. Thickening of the bronchial subepithelial layer is a contributing factor to asthma severity for which no current treatment exists. Airway epithelium acts as an initial defence barrier to inhaled spores, orchestrating an inflammatory response and contributing to subepithelial fibrosis. Objective We aimed to analyse the production of pro‐fibrogenic factors by airway epithelium in response to A fumigatus, in order to propose novel anti‐fibrotic strategies for fungal‐induced asthma. Methods We assessed the induction of key pro‐fibrogenic factors, TGF‐β1, TGF‐β2, periostin and endothelin‐1, by human airway epithelial cells and in mice exposed to A fumigatus spores or secreted fungal factors. Results Aspergillus fumigatus specifically caused production of endothelin‐1 by epithelial cells in vitro but not any of the other pro‐fibrogenic factors assessed. A fumigatus also induced endothelin‐1 in murine lungs, associated with extensive inflammation and airway remodelling. Using a selective endothelin‐1 receptor antagonist, we demonstrated for the first time that endothelin‐1 drives many features of airway remodelling and inflammation elicited by A fumigatus. Conclusion Our findings are consistent with the hypothesis that elevated endothelin‐1 levels contribute to subepithelial thickening and highlight this factor as a possible therapeutic target for difficult‐to‐treat fungal‐induced asthma.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 92%

Endothelin‐1 mediates Aspergillus fumigatus‐induced airway inflammation and remodelling

Labram

Namvar

Hussell

et al. 2019

Clin Experimental Allergy

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“…This has uncontrollable effects on the physiology of the cultured cells and therefore requires careful interpretation of the data and verification of the results in more physiological settings (see (14) and references therein). Furthermore, only very few studies were undertaken to obtain a comprehensive characterization of the molecular response of AEC II to the fungal insult (18).…”

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confidence: 99%

Quantitative Analysis of Proteome Modulations in Alveolar Epithelial Type II Cells in Response to Pulmonary Aspergillus fumigatus Infection

Seddigh

Bracht

Molinier‐Frenkel

et al. 2017

Molecular & Cellular Proteomics

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The ubiquitous mold threatens immunosuppressed patients as inducer of lethal invasive aspergillosis. conidia are airborne and reach the alveoli, where they encounter alveolar epithelial cells (AEC). Previous studies reported the importance of the surfactant-producing AEC II during infection experiments using cell lines. We established a negative isolation protocol yielding untouched primary murine AEC II with a purity >90%, allowing analyses of the cells, which encountered the mold By label-free proteome analysis of AEC II isolated from mice 24h after or mock infection we quantified 2256 proteins and found 154 proteins to be significantly differentially abundant between both groups (ANOVA value ≤ 0.01, ratio of means ≥1.5 or ≤0.67, quantified with ≥2 peptides). Most of these proteins were higher abundant in the infected condition and reflected a comprehensive activation of AEC II on interaction with This was especially represented by proteins related to oxidative phosphorylation, hence energy production. However, the most strongly induced protein was the l-amino acid oxidase (LAAO) Interleukin 4 induced 1 (IL4I1) with a 42.9 fold higher abundance (ANOVA value 2.91). IL4I1 has previously been found in B cells, macrophages, dendritic cells and rare neurons. Increased IL4I1 abundance in AEC II was confirmed by qPCR, Western blot and immunohistology. Furthermore, infected lungs showed high levels of IL4I1 metabolic products. Importantly, higher IL4I1 abundance was also confirmed in lung tissue from human aspergilloma. Because LAAO are key enzymes for bactericidal product generation, AEC II might actively participate in pathogen defense. We provide insights into proteome changes of primary AEC II thereby opening new avenues to analyze the molecular changes of this central lung cell on infectious threats. Data are available ProteomeXchange with identifier PXD005834.

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“…Analysis of changes in this intrinsic antiviral pathway in response to IBV infection is critical to elucidate IBV-host interaction. In this study, we examined IBV infection induced response in human lung epithelial A549 cells, a well characterized cell system that responds to infection robustly and has been extensively used to investigate innate immune response of pathogens, including but not limited to Ebola virus [40], Influenza A virus [41][42][43], Aspergillus fumigatus [44], Newcastle Disease Virus [45]. Our results generated a number of interesting observations.…”

Section: Discussionmentioning

confidence: 94%

Next-Generation Sequencing Analysis of Cellular Response to Influenza B Virus Infection

Sheng

Huang

Liu

et al. 2020

Viruses

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Influenza B virus (IBV) is a respiratory pathogen that infects humans and causes seasonal influenza epidemics. However, cellular response to IBV infection in humans and mechanisms of host-mediated restriction of IBV replication are not thoroughly understood. In this study, we used next-generation sequencing (NGS) to perform transcriptome profiling of IBV-infected human lung epithelial A549 cells at 0, 6, 12, and 24 h post infection (hpi) and characterized the cellular gene expression dynamics. We observed that more than 4000 host genes were differentially regulated during the study period, which included up regulation of genes encoding proteins, having a role in the innate antiviral immune responses, immune activation, cellular metabolism, autophagy, and apoptosis, as well as down regulation of genes involved in mitosis and cell proliferation. Further analysis of RNA-Seq data coupled with RT-qPCR validation collectively showed that double-strand RNA recognition pathways, including retinoic acid-inducible gene I (RIG-I) and Toll-like receptor 3 (TLR3), were substantially activated following IBV infection. Taken together, these results provide important initial insights into the intimate interaction between IBV and lung epithelial cells, which can be further explored towards elucidation of the cellular mechanisms in restriction or elimination of IBV infections in humans.

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Transcriptome Profiles of Human Lung Epithelial Cells A549 Interacting with Aspergillus fumigatus by RNA-Seq

Cited by 46 publications

References 46 publications

Endothelin‐1 mediates Aspergillus fumigatus‐induced airway inflammation and remodelling

Endothelin‐1 mediates Aspergillus fumigatus‐induced airway inflammation and remodelling

Quantitative Analysis of Proteome Modulations in Alveolar Epithelial Type II Cells in Response to Pulmonary Aspergillus fumigatus Infection

Next-Generation Sequencing Analysis of Cellular Response to Influenza B Virus Infection

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