Transcriptome Analysis Reveals Unfolded Protein Response Was Induced During the Early Stage of Infection in A549 Cells.

Chenglong Rao, Chan Mao, Yupei Xia, Meijuan Zhang, Zhiqiang Hu, Siqi Yuan, Wenbo Yang, Jingmin Yan, Ling Deng, Xiaolian Cai, Xuhu Mao, Qian Li, Yaling Liao
Author Information
  1. Chenglong Rao: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.
  2. Chan Mao: Department of Pharmacy, Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
  3. Yupei Xia: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.
  4. Meijuan Zhang: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.
  5. Zhiqiang Hu: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.
  6. Siqi Yuan: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.
  7. Wenbo Yang: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.
  8. Jingmin Yan: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.
  9. Ling Deng: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.
  10. Xiaolian Cai: Department of Cardiology, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, China.
  11. Xuhu Mao: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.
  12. Qian Li: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.
  13. Yaling Liao: Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University), Chongqing, China.

Abstract

is a zoonotic pathogen that usually affects patients' lungs and causes serious melioidosis. The interaction of with its hosts is complex, and cellular response to infection in humans still remains to be elucidated. In this study, transcriptomic profiling of -infected human lung epithelial A549 cells was performed to characterize the cellular response dynamics during the early infection (EI) stage. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using the online databases DAVID 6.8 and KOBAS 3.0. Real-time quantitative PCR and western blot were used for validation experiments. Compared with the negative control group (NC), a set of 36 common genes varied over time with a cut-off level of 1.5-fold change, and a -value < 0.05 was identified. Bioinformatics analysis indicated that the PERK-mediated unfolded protein response (UPR) was enriched as the most noteworthy biological process category, which was enriched as a branch of UPR in the signaling pathway of protein processing in the endoplasmic reticulum. Other categories, such as inflammatory responses, cell migration, and apoptosis, were also focused. The molecular chaperone Bip (GRP78), PERK, and PERK sensor-dependent phosphorylation of eIF2α (p-eIF2α) and ATF4 were verified to be increasing over time during the EI stage, suggesting that infection activated the PERK-mediated UPR in A549 cells. Collectively, these results provide important initial insights into the intimate interaction between and lung epithelial cells, which can be further explored toward the elucidation of the cellular mechanisms of infections in humans.

Keywords

References

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Word Cloud

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