{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:01:11Z","timestamp":1793152871564,"version":"4.5.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"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":["mBio"],"published-print":{"date-parts":[[2025,11,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Chlamydia trachomatis<\/jats:italic>\n                      , an obligate intracellular pathogen, manipulates host cells to evade immune detection, contributing to sexually transmitted diseases with severe complications. Neutrophils, short-lived effector cells, form the first line of innate immune defense against infection. Here, we demonstrate that\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      infection extends the lifespan of human neutrophils, creating a cellular niche for its own survival. Lifespan extension involves the neutrophil PI3K\/Akt- and the NF-\u03baB signaling pathways. In addition, infection activates the necroptotic effector receptor-interacting protein kinase 3 (RIP3) without inducing cell death. Instead, RIP3 stabilizes the anti-apoptotic protein Mcl-1, enhancing neutrophil survival. This extended survival of neutrophils correlates with an increased number of infectious\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      particles. Mcl-1 plays a critical role in neutrophil survival, lifespan extension, and\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      survival. Notably, inhibiting RIP3 reduces Mcl-1 levels in neutrophils without affecting their survival. Under these conditions, however,\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      load increases, and the dependence on Mcl-1 is bypassed. Our data reveal a new role for necroptosis in neutrophil defense against intracellular\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      , highlighting a complex interplay between RIP3 and Mcl-1 that extends neutrophil lifespan and enhances\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      survival within these hostile cells.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        This study reveals how\n                        <jats:italic toggle=\"yes\">Chlamydia trachomatis<\/jats:italic>\n                        , a common sexually transmitted bacterium, manipulates the body\u2019s first immune responders, the neutrophils, to aid its own survival. Normally short-lived, neutrophils live longer when infected by\n                        <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                        , creating a safe environment for the bacteria. This lifespan extension is driven by specific cell survival signals and a protein called RIP3, which surprisingly does not cause cell death here, but helps stabilize another protein, Mcl-1, that keeps neutrophils alive. Blocking RIP3 reduces Mcl-1, but\n                        <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                        still manages to survive, suggesting it can adapt to changes in the host environment. These findings uncover a new layer of complexity in how our immune system interacts with infections and could inform future strategies for treating\n                        <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                        and similar infections.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02098-25","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T13:11:22Z","timestamp":1759756282000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["<i>Chlamydia trachomatis<\/i>\n                    subverts neutrophil cell death pathways through RIP3 and Mcl-1 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