Olmos, M. | bioRxiv Science

bioRxiv2026

{triangleup}9-Tetrahydrocannabinol exposure shifts eosinophil and macrophage transcriptional programs towards an anti-inflammatory phenotype in helminth infection

Cannabis use is increasing globally, yet the immunological effects of {Delta}9-tetrahydrocannabinol (THC), the main intoxicating component of cannabis, remain incompletely understood. 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 Nippostrongylus brasiliensis (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 and IFN{gamma} secretion in splenocytes from THC-treated infected mice. Bulk RNA sequencing showed that THC shifted lung eosinophils and CD11c 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. Summary SentenceTHC reshapes helminth-induced type 2 inflammation by restraining inflammatory leukocyte responses and reprogramming lung eosinophils and macrophages.

immunology↗

bioRxiv2025

Arabidopsis thaliana Iron Superoxide Dismutase FeSOD1 Protects ARGONAUTE 1 in a Copper-Dependent Manner

Copper (Cu) deficiency compromises plant growth and limits crop productivity. Plants respond to Cu scarcity by activating the expression of several microRNAs, known as Cu-miRNAs, which degrade mRNAs from various cuproproteins to conserve Cu. Cu-miRNAs, like most plant miRNAs, associate with ARGONAUTE 1 (AGO1), the primary effector protein of miRNA-mediated gene silencing pathways, whose function is typically modulated by interacting proteins acting as cofactors. However, how AGO1 is regulated and functions under Cu deficiency remains unknown. Here, we searched for AGO1 interactors in Arabidopsis thaliana plants expressing a functional AGO1 protein tagged with the Twin-Strep-tag (TST) polypeptide, grown under Cu-sufficient or Cu-deficient conditions. TST-AGO1 complexes were affinity-purified, and proteins were identified using tandem mass spectrometry. Interestingly, the iron superoxide dismutase 1 (FeSOD1) encoded by FSD1, was enriched in TST-AGO1 complexes purified from plants grown under Cu deficiency. Moreover, fsd1-2 mutant plants showed reduced levels of AGO1 compared to wild-type plants under Cu sufficiency, while both Cu-miRNA-specific and general AGO1 target mRNAs accumulated to higher levels in fsd1-2 plants under both Cu-deficient and Cu-sufficient conditions compared to wild-type plants. These findings suggest that FeSOD1 is essential for proper AGO1 function, and that its superoxide dismutase activity, which mitigates oxidative stress, enhances AGO1 stability, particularly under Cu deficiency. HIGHLIGHTAGO1 is essential for Cu-deficiency responses but is sensitive to oxidative stress. FeSOD1 interacts with AGO1 and protects it from superoxide radical-induced degradation, thereby preserving miRNA-mediated gene silencing pathways.

plant biology↗