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The neuroimmune interactions between peripheral and central immune systems in angiostrongyliasis remain unclear. In this study, significant infiltration of eosinophils, myeloid cells, macrophages, neutrophils, and Ly6C monocytes is observed in the brains of AC\u2010infected mice, with macrophages being the most abundant. RNA\u2010seq and SMART\u2010seq analysis of pattern recognition receptor (PRR) and DNA sensor gene sets revealed a marked increase in Z\u2010DNA binding protein 1 (Zbp1) expression in infected mice. Confocal microscopy, RT\u2010qPCR, western blotting, and immunohistochemistry further confirmed that Zbp1 is specifically upregulated in macrophages and microglia. Using Zbp1\u2010knockout mice and flow cytometry, it is found that knockout of Zbp1 enhanced lymphocyte infiltration and natural killer cell cytotoxicity, modulating the immune microenvironment in the central nervous system\u00a0(CNS) during AC infection. Mechanistically, it is revealed that in macrophage Zbp1 directly binds to receptor\u2010interacting protein 3 (RIP3) to promote its phosphorylation, subsequently facilitating the phosphorylation of mixed lineage kinase domain\u2010like protein (Mlkl). The activated Zbp1\u2010pRIP3\u2010pMlkl axis leads to necroptosis and upregulates pro\u2010inflammatory cytokines including TNF\u2010\u03b1, IL\u20101\u03b1, CXCL9, CXCL10 in macrophages, which recruits and activates immune cells. These findings offer new insights into the pathogenic mechanisms of angiostrongyliasis and suggest potential therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202413675","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T05:09:37Z","timestamp":1737695377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Innate Immune Sensor Zbp1 Mediates Central Nervous System Inflammation Induced by\n                    <i>Angiostrongylus Cantonensis<\/i>\n                    by Promoting Macrophage Inflammatory Phenotypes"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3004-8481","authenticated-orcid":false,"given":"Hongli","family":"Zhou","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Disease Control (Sun Yat\u2010Sen University) Ministry of Education  Guangzhou Guangdong 510080 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