{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:16:40Z","timestamp":1785424600321,"version":"3.56.0"},"posted":{"date-parts":[[2025,10,7]]},"group-title":"Immunology","reference-count":81,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["1R35GM154838"],"award-info":[{"award-number":["1R35GM154838"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Patients with systemic lupus erythematosus (SLE) are susceptible to bacterial infections, but the underlying dysfunction remains unclear. We found that\n                  <jats:italic>Staphylococcus aureus<\/jats:italic>\n                  triggers mitochondria-dependent suicidal NETosis via lactate sensing in healthy neutrophils, but this response is defective in SLE. Herein, we show that chronic Toll-like receptor (TLR) 7\/9 signaling represses mitochondrial lactate dehydrogenase B (LDHB), thereby impairing lactate sensing and downstream suicidal NETosis. Instead, SLE neutrophils default to vital NET release; a less bactericidal, type I interferon (IFN)-driven process amplified by staphylococcal pore-forming toxins and sustained by elevated systemic IFN\u03b1 levels observed in SLE. Combined treatment with hydroxychloroquine (HCQ) and interferon-alpha\/beta receptor (IFNAR) blockade restores LDHB expression, NET homeostasis, and bacterial clearance in lupus-prone mice. Neutrophils from SLE patients exhibit similar defects, which are reversed by HCQ and the IFNAR-blocking antibody anifrolumab. These findings identify a clinically actionable immunometabolic checkpoint linking chronic autoimmune signaling to defective antibacterial defense in SLE.\n                <\/jats:p>","DOI":"10.1101\/2025.10.07.680928","type":"posted-content","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T02:20:14Z","timestamp":1759890014000},"source":"Crossref","is-referenced-by-count":1,"title":["A TLR7\/9-IFN\u03b1-LDHB axis drives vital NET release and compromises antibacterial defense in lupus"],"prefix":"10.64898","author":[{"given":"Eden G.","family":"TenBarge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley D.","family":"Wise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan L.","family":"Hetzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene 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