Δ9-Tetrahydrocannabinol exposure shifts eosinophil and macrophage transcriptional programs towards an anti-inflammatory phenotype in helminth infection.

Jennett J.; Olmos M.; Lam K.; Midou S.; DiPatrizio N.; Nair M. · Journal of leukocyte biology · 2026

**Background & Methods** This experimental study investigated the immunological effects of Δ9-tetrahydrocannabinol (THC) on helminth infection responses using C57BL/6J mice. Mice received THC (5 mg/kg/day) or vehicle control for 14 days prior to infection with Nipostrongylus brasiliensis, with assessment of parasite burden, innate immune cell populations, T cell responses, and transcriptional changes in lung eosinophils and macrophages via bulk RNA sequencing. **Key Findings** • THC exposure selectively reduced infection-induced circulating eosinophils and monocytes while increasing regulatory T cells, without altering parasite burden or infection-associated weight loss. • RNA sequencing revealed THC shifted lung eosinophils and CD11c+ macrophages from pro-inflammatory, fibrotic, and costimulatory transcriptional programs toward stress-response and metabolic-adaptive pathways; within macrophages, THC reduced CD80 expression while increasing MHC class II and antigen presentation genes. • THC-treated infected mice demonstrated reduced TNF-α and IFN-γ secretion from splenocytes, and immunofluorescence analysis showed THC mitigated infection-associated lung collagen loss, suggesting protection against tissue remodeling. **Dosage & Administration** 5 mg/kg/day THC administered for 14 days prior to helminth infection. Route of administration not specified. **Safety & Adverse Effects** Not reported. **Evidence Quality** This is a preclinical murine model study with important limitations. The findings are restricted to a single helminth species and mouse strain, limiting generalizability to human infections. No direct mechanistic validation of transcriptional findings was performed (e.g., protein-level confirmation, functional assays). The study demonstrates correlation between THC exposure and altered immune transcriptional programs but does not establish causation or identify specific endocannabinoid receptor mechanisms. Translation to human immunity is uncertain given species differences and the use of a single THC dose. The work provides preliminary mechanistic insight into endocannabinoid signaling in type 2 inflammation but requires substantial additional validation before clinical applicability can be determined. Classification as a review article by the authors suggests this may represent a synthesis of findings rather than primary experimental data.

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