LncRNA SBF2-AS1 Regulates Pyroptosis to Promote Chlamydia trachomatis Growth Through miR-196b-5p/RIPK2 Axis

Pyroptosis enables host cells to eliminate intracellular pathogens effectively. However, how <i>Chlamydia trachomatis</i> (<i>C. trachomatis</i>) evades host pyroptosis remains unclear. This study reveals that <i>C. trachomatis</i> exploits the host Long non-coding RNA (lncRNA) SBF2-AS1 as a key factor to regulate the host pyroptosis. The SBF2-AS1 was significantly upregulated during <i>C. trachomatis</i> infection. Knockdown of SBF2-AS1 activated NLRP3/caspase-1/GSDMD pyroptosis pathway. Mechanistically, it verified that SBF2-AS1 functions as a competing endogenous RNA for miR-196b-5p targeting RIPK2 through dual-luciferase reporter gene assay. We further identified the interaction between RIPK2 and Caspase-1 by Co-immunoprecipitation (Co-IP). Silencing SBF2-AS1 or RIPK2, as well as overexpressing miR-196b-5p, triggered pyroptosis and suppressed the replication of <i>C. trachomatis</i>. In conclusion, <i>C. trachomatis</i> upregulates SBF2-AS1 to increase RIPK2 by binding miR-196b-5p, which shields against pyroptosis mediated by Caspase-1 to promote its proliferation. These results uncover a novel mechanism of pathogen-host interaction and provide insights for developing new therapeutic strategies against <i>C. trachomatis</i> infection.