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Transl. Med."],"published-print":{"date-parts":[[2025,12,24]]},"abstract":"<jats:p>Sepsis-associated secondary infection often leads to a high mortality rate. Dysfunctional macrophages are primary contributors to inadequate antimicrobial defense in patients with sepsis-associated immunosuppression. Rejuvenating macrophage antibacterial capacity is beneficial for host defense against secondary infection. Here, we developed \u201cBATMAN\u201d (bacteria-targeted transformable macrophage nanorejuvenator), a self-assembling peptide nanoparticle to tackle sepsis-associated secondary infection by coordinating the arrest of invasive bacteria and rejuvenation of dysfunctional macrophages. BATMAN comprises a bacteria-targeting ubiquicidin peptide domain, bacterial lipase\u2013sensitive cholesteryl hemisuccinate, an assembly-driving FFVLK domain, and the immunoglobulin G\u2013derived tuftsin peptide. Upon activation by bacterial lipase, the particles undergo an inside-out transformation and assembly to expose and cluster the concealed tuftsin peptides for interaction with macrophage Fc\u03b3 receptors. Interaction of tuftsin clusters with macrophage Fc\u03b3 receptors enhanced bacterial phagocytosis and drove macrophage repolarization. In a cecal slurry\u2013induced septic mouse model with secondary pulmonary infection, BATMAN treatment improved survival rates and rejuvenated the sepsis-compromised immune response to address polymicrobial- and multidrug-resistant pathogen\u2013induced pulmonary infections. These findings suggest that BATMAN holds promise for further development as a therapeutic alternative for sepsis-associated secondary infection.<\/jats:p>","DOI":"10.1126\/scitranslmed.adv0313","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T18:58:10Z","timestamp":1766602690000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Fc\u03b3R-targeted tuftsin clusters rejuvenate macrophages in preclinical sepsis\u2013associated secondary infection"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7278-5869","authenticated-orcid":true,"given":"Guangchao","family":"Qing","sequence":"first","affiliation":[{"name":"Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China."},{"name":"Department of Laboratory Medicine, Chongqing General Hospital, School of Medicine, Chongqing University, Chongqing 400044, P. R. China."},{"name":"University of Chinese Academy of Sciences, Beijing 100049, P. R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1247-6319","authenticated-orcid":true,"given":"Yuxuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Controllable Nanopharmaceuticals, Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China."},{"name":"University of Chinese Academy of Sciences, Beijing 100049, P. R. 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