bims-inflin Biomed News
on Inflammasome and infection
Issue of 2023–09–10
two papers selected by
Juliane Cristina Ribeiro Fernandes, Faculdade de Medicina de Ribeirão Preto
  1. Viral sensing by epithelial cells involves PKR- and caspase-3-dependent generation of gasdermin E pores.
  2. In Silico Identification and Validation of Pyroptosis-Related Genes in Chlamydia Respiratory Infection.
  1. iScience. 2023 Sep 15. 26(9): 107698
    Viral sensing by epithelial cells involves PKR- and caspase-3-dependent generation of gasdermin E pores.
    Coralie Guy, Marcin Baran, Pau Ribó-Molina, Bernadette G van den Hoogen, Andrew G Bowie.
      Viral sensing in myeloid cells involves inflammasome activation leading to gasdermin pore formation, cytokine release, and cell death. However, less is known about viral sensing in barrier epithelial cells, which are critical to the innate immune response to RNA viruses. Here, we show that poly(I:C), a mimic of viral dsRNA, is sensed by NLRP1 in human bronchial epithelial cells, leading to inflammasome-dependent gasdermin D (GSDMD) pore formation via caspase-1. DsRNA also stimulated a parallel sensing pathway via PKR which activated caspase-3 to cleave gasdermin E (GSDME) to form active pores. Influenza A virus (IAV) infection of cells caused GSDME activation, cytokine release, and cell death, in a PKR-dependent but NLRP1-independent manner, involving caspase-8 and caspase-3. Suppression of GSDMD and GSDME expression increased IAV replication. These data clarify mechanisms of gasdermin cleavage in response to viral sensing and reveal that gasdermin pore formation is intrinsically antiviral in human epithelial cells.
    Keywords:  Immunology; Virology
    DOI:  https://doi.org/10.1016/j.isci.2023.107698
  2. Int J Mol Sci. 2023 Sep 01. pii: 13570. [Epub ahead of print]24(17):
    In Silico Identification and Validation of Pyroptosis-Related Genes in Chlamydia Respiratory Infection.
    Ruoyuan Sun, Wenjing Zheng, Shuaini Yang, Jiajia Zeng, Yuqing Tuo, Lu Tan, Hong Zhang, Hong Bai.
      The incidence of Chlamydia trachomatis respiratory infection is increasing, and its pathogenesis is still unclear. Pyroptosis, as a mode of inflammatory cell death, plays a vital role in the occurrence and development of Chlamydia trachomatis respiratory infection. In this study, the potential pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection were identified by constructing a mouse model of C. muridarum infection combined with bioinformatics analysis. Through in-depth analysis of the RNA sequencing data, 13 differentially expressed pyroptosis-related genes were screened, including 1 downregulated gene and 12 upregulated genes. Gene ontology (GO) analysis showed that these genes mainly regulate inflammatory responses and produce IL-1β. Protein-protein interaction network analysis identified eight hub genes of interest: Tnf, Tlr2, Il1b, Nlrp3, Tlr9, Mefv, Zbp1 and Tnfaip3. Through quantitative real-time PCR (qPCR) analysis, we found that the expression of these genes in the lungs of C. muridarum-infected mice was significantly reduced, consistent with the bioinformatics results. At the same time, we detected elevated levels of caspase-3, gasdermin D and gasdermin E proteins in the lungs of C. muridarum-infected mice, demonstrating that Chlamydia trachomatis infection does induce pyroptosis. We then predicted nine miRNAs targeting these hub genes and constructed a key competitive endogenous RNA (ceRNA) network. In summary, we identified six key pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection and constructed a ceRNA network associated with these genes. These findings will improve understanding of the molecular mechanisms underlying pyroptosis in Chlamydia trachomatis respiratory infections.
    Keywords:  Chlamydia trachomatis infection; competitive endogenous RNA regulatory network; immune infiltration; inflammatory death; pyroptosis
    DOI:  https://doi.org/10.3390/ijms241713570
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