Angiostrongylus cantonensis (A. cantonensis) is a foodborne parasite that can invade the central nervous system (CNS), resulting in eosinophilic meningitis (EM). However, the mechanism by which A. cantonensis causes eosinophilic infiltration into CNS is not well understood. In this study eosinophilic infiltration into the CNS caused by A. cantonensis was assessed based on eosinophil counts and evaluation of interleukin (IL)-5 and -13 levels by real-time PCR in brain of Balb/c mice. The expression and activation of IL-17A, IL17 receptor (IL-17R A), and IL-17RC and the related signaling molecules nuclear factor (NF)-κB1, NF-κB2, NF-κB activator (Act)1, tumor necrosis factor receptor-associated factor (Traf)5, and Traf6 during A. cantonensis infection in brain tissue of Balb/c mice were examined by real-time, western blotting and immunofluroence. A. cantonensis-infected Balb/c mice were treated with IL-17A neutralizing antibody to evaluate the role of IL17A in eosinophil accumulation in the CNS. Our results showed A. cantonensis infection caused eosinophil accumulation and alterations in IL-5 and -13 levels. The expression of IL-17A and -17RA, Act1, and Traf6 but not of IL-17RC and Traf5 was upregulated during infection; this was accompanied by NF-κB1 and -κB2 activation. Importantly, application of IL-17A neutralizing antibody attenuated eosinophil accumulation in CNS and reversed the changes in IL-5 and -13 expression caused by A. cantonensis infection. Additionally, IL-17RA and Traf6 levels decreased, which was accompanied by NF-κB inactivation. IL-17A plays an important role in EM caused by A. cantonensis, possibly through activation of NF-κB via the IL-17RA/Traf6 signaling pathway. These findings highlight the potential for using IL-17A neutralizing antibody as a therapeutic strategy for the treatment of EM.

Background: Pathogenic variants in DEAF1 cause DEAF1-associated neurodevelopmental disorders (DAND) with autosomal-dominant (typically de novo ) and autosomal-recessive (biallelic) presentations. We sought to characterize five unrelated children with de novo DEAF1 variants, define epilepsy phenotypes, and refine inheritance-specific genotype–phenotype architecture with developmental context. Methods: Trio-based whole-exome sequencing with Sanger confirmation was performed in five unrelated children. Missense variants were evaluated using structural modeling and in silico stability/physicochemical assessments. DEAF1 expression was examined using GTEx, the Human Protein Atlas, BrainSpan, Evo-devo mammalian organ transcriptomes, and single-cell brain organoid datasets. A systematic literature review (inception–March 2026) curated eligible cases for intersection-based UpSet analyses and system-level stacked summaries. Results: Five unrelated children carried heterozygous de novo DEAF1 missense variants; four mapped to the SAND domain (p.Leu203Pro, p.Gly212Ser, p.Ile228Met, p.Leu272Ser) and one was N-terminal (p.Ala29Pro). p.Ala29Pro and p.Ile228Met were not recorded in ClinVar, HGMD Professional, or the reviewed literature. All five patients had intellectual disability/developmental delay with prominent expressive language impairment and motor delay/hypotonia. Epilepsy was observed in all patients, with onset ranging from 7 months to 2 years 8 months, and focal impaired consciousness seizures (FIC) predominated. EEG abnormalities were observed in 4 of the 5 patients, and all five were seizure-free on anti-seizure medications at the last follow-up. Structural modeling suggested variant-dependent perturbations, particularly among SAND-domain substitutions, but these findings remain computational predictions. Expression analyses supported brain-enriched, developmentally regulated DEAF1 expression and broad neuronal/progenitor expression in human brain organoids. A literature review identified 62 individuals from 15 studies; combined with our cohort, 67 individuals were analyzed ( de novo n = 52; biallelic n = 15). De novo variants clustered within/around the SAND domain, whereas biallelic variants were more broadly distributed. UpSet and stacked-bar analyses revealed a shared neurodevelopmental core but distinct co-occurrence patterns, with autism/epilepsy shaping dominant intersections in de novo cases and microcephaly/MRI abnormalities contributing more prominently in biallelic disease. Conclusions: Our study refines the de novo clinical and allelic spectrum of DAND and delineates inheritance-specific genotype–phenotype architecture with developmental and cellular context.