In Silico Identification and Validation of Pyroptosis-Related Genes in Chlamydia Respiratory Infection

The incidence of <i>Chlamydia trachomatis</i> 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 <i>Chlamydia trachomatis</i> respiratory infection. In this study, the potential pyroptosis-related genes involved in <i>Chlamydia trachomatis</i> respiratory infection were identified by constructing a mouse model of <i>C. muridarum</i> 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: <i>Tnf</i>, <i>Tlr2</i>, <i>Il1b</i>, <i>Nlrp3</i>, <i>Tlr9</i>, <i>Mefv</i>, <i>Zbp1</i> and <i>Tnfaip3</i>. Through quantitative real-time PCR (qPCR) analysis, we found that the expression of these genes in the lungs of <i>C. muridarum</i>-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 <i>C. muridarum</i>-infected mice, demonstrating that <i>Chlamydia trachomatis</i> 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 <i>Chlamydia trachomatis</i> respiratory infection and constructed a ceRNA network associated with these genes. These findings will improve understanding of the molecular mechanisms underlying pyroptosis in <i>Chlamydia trachomatis</i> respiratory infections.