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Given prior evidence that endocannabinoid signaling influences helminth immunity and type 2 inflammation, we investigated how sustained THC exposure alters immune responses to the helminth\n                  <jats:italic>Nippostrongylus brasiliensis<\/jats:italic>\n                  (Nb), which infects the lung and small intestine of mice. C57BL\/6J mice were treated with THC (5 mg\/kg\/day) or vehicle for 14 days prior to helminth infection and assessed for parasite burden, innate immune cell and T cell responses, and transcriptional changes in lung eosinophils and macrophages. THC exposure did not significantly alter infection-associated weight loss or helminth burden; however, THC selectively restrained infection-induced circulating eosinophils and monocytes while increasing regulatory T cells. T cell activation assays showed reduced TNF\u03b1 and IFN\u03b3 secretion in splenocytes from THC-treated infected mice. Bulk RNA sequencing showed that THC shifted lung eosinophils and CD11c\u207a lung macrophage-enriched cells from inflammatory, fibrotic, and costimulatory pathways toward stress and metabolic-adaptive transcriptional programs. Within the infected macrophage-enriched population, THC reduced CD80 expression while increasing MHC class II and antigen presentation-associated genes, suggesting a potential shift in macrophage-mediated T cell activation. Consistent with altered inflammatory and tissue remodeling-associated programs, immunofluorescent staining showed that THC mitigated infection-associated loss of lung collagen. Collectively, these findings indicate that THC reshapes the immune response to helminth infection by restraining innate and T cell effector responses while altering lung eosinophil and macrophage activation programs.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary Sentence<\/jats:title>\n                  <jats:p>THC reshapes helminth-induced type 2 inflammation by restraining inflammatory leukocyte responses and reprogramming lung eosinophils and macrophages.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.11.729983","type":"posted-content","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T16:25:13Z","timestamp":1781281513000},"source":"Crossref","is-referenced-by-count":0,"title":["\u0394\n                  <sup>9<\/sup>\n                  -Tetrahydrocannabinol exposure shifts eosinophil and macrophage transcriptional programs towards an anti-inflammatory phenotype in helminth infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1638-275X","authenticated-orcid":false,"given":"Jennell","family":"Jennett","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Olmos","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Man","family":"Lam","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Midou","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8423-0695","authenticated-orcid":false,"given":"Nicholas V.","family":"DiPatrizio","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1807-5161","authenticated-orcid":false,"given":"Meera G.","family":"Nair","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026061518401005000_2026.06.11.729983v1.1","unstructured":"Key Substance Use and Mental Health Indicators in the United States: Results from the 2022 National Survey on Drug Use and Health."},{"key":"2026061518401005000_2026.06.11.729983v1.2","first-page":"161","article-title":"International Union of Pharmacology","volume":"54","year":"2002","journal-title":"XXVII. 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