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This review delineates the functional, metabolic, and spatial characteristics of these two phagocytic cell types and highlights their bidirectional interactions across distinct immunological phases of sepsis. Multiple intercellular conduits, including extracellular vesicles, cytokine\u2013chemokine axes, extracellular traps, and efferocytosis, mediate context-specific reprogramming of effector states, with extracellular vesicle cargo and trap degradation products emerging as diagnostic and therapeutic targets. Advances in nanomedicine now enable phase-specific manipulation of this myeloid crosstalk, attenuating pathogenic inflammation in the early phase and restoring antimicrobial competence during immunosuppression. Dissecting the spatiotemporal, metabolic, and molecular logic of neutrophil\u2013macrophage communication offers a framework for precision immunomodulation in sepsis, with potential to recalibrate the immune landscape toward controlled inflammation and durable resolution.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf152","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T12:51:55Z","timestamp":1763470315000},"source":"Crossref","is-referenced-by-count":1,"title":["Bidirectional neutrophil\u2013macrophage interactions as therapeutic leverage points in sepsis"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1133-1241","authenticated-orcid":false,"given":"Zhuo","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University , 138 Tongzipo Road, Changsha 410013 ,","place":["China"]},{"name":"Department of Laboratory Medicine, Xiangya School of Medicine, Central South University , 172 Tongzipo Road, Changsha 410013 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keqian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University , 138 Tongzipo Road, Changsha 410013 ,","place":["China"]},{"name":"Department of Laboratory Medicine, Xiangya School of Medicine, Central South University , 172 Tongzipo Road, Changsha 410013 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"2025112007585412500_qiaf152-B1","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1007\/s00134-025-07873-6","article-title":"Sepsis subphenotypes, theragnostics and personalized sepsis care","volume":"51","author":"Antcliffe","year":"2025","journal-title":"Intensive Care 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