Biology subjects

Midou, S.

Publications and source records attributed to Midou, S..

3 recordsLinked to original sources

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↗

bioRxiv2026

Helminth infection induces RELMa-dependent adipose tissue transcriptional reprogramming and protection against diet-induced obesity

Obesity, a rising epidemic in the United States, is causally associated with adipose tissue inflammation, therefore targeting this immune dysfunction offers promising therapeutic avenues. Chronic helminth infection can prevent obesity pathogenesis but there remain opportunities to determine the immune factors that mediate protection and whether long-term protection is associated with changes in the visceral adipose tissue. We optimized a mouse model of western diet-induced obesity and investigated if transient helminth infection was protective through the immunoregulatory protein RELM. Wild-type (WT) or RELM knockout (KO) C57BL/6J mice were fed a western diet of high glucose and high fat followed by infection with helminth Nippostrongylus brasiliensis, which infects the lung and small intestine but is cleared within two weeks. Infection attenuated weight gain and improved glucose tolerance even after the parasite was expelled in WT but not RELM deficient mice. This protection was associated with reduced adipocyte hypertrophy in WT mice. Adipose tissue bulk RNA sequencing and digital cell quantification indicated that RELM promoted enrichment of eosinophils and M2 macrophages and upregulated pathways associated with fatty acid oxidation, mitochondrial function, and thermogenesis, whereas RELM deficiency led to pro-inflammatory, fibrotic, and lipid accumulation transcriptional profiles. Specific genes that were changed with infection and RELM deficiency included collagen and serpin genes associated with tissue remodeling and fibrosis, and changes within the adipose tissue was confirmed by immunofluorescent staining. Together, these findings establish that helminth-induced RELM critically protects against western diet-driven obesity and associated adipose transcriptional reprogramming and tissue remodeling.

immunology↗

bioRxiv2025

Beyond Motility: A Multiparametric Fitness Assay Framework to Evaluate Anthelmintics in Nippostrongylus brasiliensis

We adapted a multiparametric fitness assay panel--including ATP quantification, larval growth, pigmentation, and cuticle permeability--to assess Nippostrongylus brasiliensis viability in vitro. To validate this system, we benchmarked two known anthelmintics with distinct modes of action: quinidine, a heme detoxification disruptor, and pyrantel pamoate, a neuromuscular antagonist. We then applied this framework to NCR247, a plant-derived heme-sequestering peptide with proposed antiparasitic activity. While the assay panel sensitively detected physiological disruption by known anthelmintics, NCR247 did not significantly impair parasite fitness across any tested parameter. These findings highlight the utility of integrated viability assays and suggest further in vivo or delivery-optimized studies may be necessary to evaluate NCR247 efficacy.

molecular biology↗