Abstract
Lung epithelial cells constitute the first defense line of host against the inhaled Aspergillus fumigatus; however, the transcriptional response of human alveolar type II epithelial cells was still unclear. Here we used RNA-Seq technology to assess the transcriptome profiles of A549 cells following direct interaction with conidia of A. fumigatus. The total number of identified genes was 19118. Compared with uninfected A549 cells, 459 genes were differentially expressed in cells co-incubated with conidia for 8 h, including 302 up-regulated genes and 157 down-regulated genes. GO and KEGG pathway enrichment analysis showed that most of the up-regulated genes were related to immune response, chemotaxis and inflammatory response and enriched in cytokine-cytokine receptor interaction, JAK-STAT and MAPK signaling pathways. The down-regulated genes were mainly enriched for terms associated with development, hemopoiesis and ion transport. Among them, EGR4 and HIST1H4J gene had the maximum of fold change in up-regulated and down-regulated genes, respectively. Fourteen up-regulated genes and three down-regulated genes were further validated and significant increase on expression of IL-6, IL-8 and TNF-α in A549 cells were confirmed by qRT-PCR during the interaction of A549 cells with A. fumigatus. Besides, western blot showed that expression of two proteins (ARC, EGR1) significantly increased in A549 cells during interaction with A. fumigatus conidia for 8h. Interference of endogenous expression of ARC or EGR1 protein in A549 cells reduced the internalization of A. fumigatus. These results provided important insights into dynamic changes of gene expression in lung epithelial cells, especially its strong immunological response against A. fumigatus infection.
Highlights
Aspergillus fumigatus is an important opportunistic fungal pathogen, widely distributed in nature including soil, decaying vegetation, compost heaps, and in most indoor environments [1,2,3]
To better elucidate the response of lung epithelial cells against A. fumigatus conidia infection at the molecular level, we used RNA-Seq analysis to determine changes in gene expression in A549 cells infected with A. fumigatus conidia
We proved that expression of three inflammatory cytokines, IL6, IL-8 and TNF-α in A549 cells augmented clearly during infection by A. fumigatus (S1 Fig)
Summary
Aspergillus fumigatus is an important opportunistic fungal pathogen, widely distributed in nature including soil, decaying vegetation, compost heaps, and in most indoor environments [1,2,3]. Human Host Transcriptome Responsing against A. fumigatus Infection air and allowing them to reach the innermost areas of the lung, including the alveoli [1, 4]. It is likely for all humans to inhale at least several hundred conidia each day [5]. Depending on the immune status of the host, Aspergillus species can cause a spectrum of diseases in humans which range from local hypersensitivity reactions to often fatal systemic mycoses [6]. A. fumigatus is responsible for approximately 90% of human Aspergillus infection [1, 7,8]
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