{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:36:26Z","timestamp":1773225386168,"version":"3.50.1"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2026,3,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Streptococcus pneumoniae<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                      ) infection induces pyroptosis in human pulmonary artery epithelial cells (HPAEpiCs), which contributes to pneumonia pathogenesis. We aimed to investigate the regulatory role of N6-methyladenosine (m\n                      <jats:sup>6<\/jats:sup>\n                      A) modification mediated by methyltransferase-like (METTL) 14 in this process and elucidate the underlying molecular mechanisms. HPAEpiCs were infected with\n                      <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                      . Cell viability was assessed using the cell counting kit-8 assay, while cytokine concentrations were measured by enzyme-linked immunosorbent assay. Pyroptosis levels were analyzed through flow cytometry and Western blot for pyroptotic protein expression. Gene expression profiles, protein-RNA interactions, and m\n                      <jats:sup>6<\/jats:sup>\n                      A methylation sites were characterized by quantitative reverse transcription-polymerase chain reaction, RNA immunoprecipitation, and dual-luciferase reporter assays.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      experiments involved intranasal administration of\n                      <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                      in mice to evaluate pulmonary pathological changes.\n                      <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                      D39\n                      <jats:italic toggle=\"yes\">-<\/jats:italic>\n                      infected HPAEpiCs exhibited enhanced pyroptosis and adhesive\/invasive capabilities, accompanied by elevated m\n                      <jats:sup>6<\/jats:sup>\n                      A modification mediated by METTL14. In addition, METTL14 inhibition suppressed pyroptosis and adhesive\/invasive capabilities and ameliorated\n                      <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                      D39\n                      <jats:italic toggle=\"yes\">-<\/jats:italic>\n                      induced lung injury. Notably, NEK7 overexpression reversed the pyroptosis reduction caused by METTL14 knockout. Mechanistically, the METTL14\/insulin-like growth factor 2 mRNA-binding proteins (IGF2BP)1 m\n                      <jats:sup>6<\/jats:sup>\n                      A regulatory axis modulated NEK7 mRNA stability through m\n                      <jats:sup>6<\/jats:sup>\n                      A-dependent post-transcriptional regulation. The METTL14\/IGF2BP1 m\n                      <jats:sup>6<\/jats:sup>\n                      A regulatory axis promoted\n                      <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                      D39\n                      <jats:italic toggle=\"yes\">-<\/jats:italic>\n                      induced pyroptosis by stabilizing NEK7 mRNA transcripts. Targeting this m\n                      <jats:sup>6<\/jats:sup>\n                      A regulatory pathway represents a potential therapeutic strategy for managing\n                      <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                      D39\n                      <jats:italic toggle=\"yes\">-<\/jats:italic>\n                      induced pneumonia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00474-25","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:00:27Z","timestamp":1770904827000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["METTL14\/IGF2BP1 m\n                    <sup>6<\/sup>\n                    A axis promotes pyroptosis in\n                    <i>Streptococcus pneumoniae<\/i>\n                    -induced pneumonia by regulating NEK7 mRNA 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