{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:29:02Z","timestamp":1792459742310,"version":"4.5.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Natural Scientific Foundation of China","award":["81860016"],"award-info":[{"award-number":["81860016"]}]},{"name":"Scientific Research Funding Project of Ningxia Medical University","award":["XT2024032"],"award-info":[{"award-number":["XT2024032"]}]},{"name":"Natural Science Foundation of Ningxia Hui Autonomous Region in 2024","award":["2024AAC05083"],"award-info":[{"award-number":["2024AAC05083"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The inflammatory cytokine storm is a hallmark of sepsis and is highly correlated with organ injury. Therefore, inhibiting inflammatory cytokine production is a straightforward strategy for effectively treating this disease. In this study, we found that microvesicles from lipopolysaccharide (LPS)-primed macrophages could transfer mitochondria to other macrophages and alter their biological functions. Microvesicles were isolated from LPS-primed macrophages and characterized by transmission electron microscopy. The function of microvesicle-transferred mitochondria in macrophages was evaluated by assessing the expression levels of inflammatory cytokines using immunofluorescent and quantitative real-time polymerase chain reaction (RT-qPCR) assays, and metabonomics using\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      models. Microvesicles derived from LPS-primed macrophages were able to transfer mitochondria to other macrophages. Functionally, these microvesicles induced classical activated macrophage (M1) polarization, reduced phagocytic capacity, altered mitochondrial homeostasis and metabolism in macrophages, and ultimately caused organ injury\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Mechanistically, we demonstrated that metformin could inhibit the microvesicle-transferred mitochondrial reactive oxygen species (mtROS) and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-Interferon Beta (IFN-\u03b2) signaling activity, subsequently reducing inflammatory cytokine production. Our findings suggest that mtROS production is a critical cellular response in the inflammatory cytokine storm of sepsis, and the cGAS-STING-IFN-\u03b2 signaling pathway may be a novel therapeutic target for sepsis treatment.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Sepsis remains lethal due to an uncontrolled \u201ccytokine storm\u201d damaging organs, yet specific treatments are lacking. Our study reveals a critical new mechanism: mitochondria transferred via microvesicles from stressed macrophages trigger this storm. These are transferred via microvesicles from stressed macrophages and trigger this storm. These transferred mitochondria reprogram recipient cells into damaging inflammatory (M1) states, reduce infection-fighting ability, disrupt metabolism, and cause organ injury. Importantly, we identify the mtROS\/cGAS-STING-IFN-\u03b2 pathway as the specific driver of inflammation within this process. Demonstrating that metformin blocks this pathway and reduces cytokine production reveals a novel strategy targeting the fundamental cause. This work is significant as it identifies mtROS\/cGAS-STING-IFN-\u03b2 as a key therapeutic target and repurposes metformin for potential sepsis treatment.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00781-25","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T13:01:47Z","timestamp":1756990907000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Microvesicle-transferred mitochondria trigger cGAS-STING and reprogram metabolism of macrophages in sepsis"],"prefix":"10.1128","volume":"13","author":[{"given":"Ting","family":"Ji","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02h8a1848","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Key Laboratory of Ningxia Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical 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