Foxp3⁺ Regulatory T Cells Restrain Th1 Response Shielding the Brain from Lethal Inflammatory Damage during Cryptococcal Meningoencephalitis.

ABSTRACT: Inflammatory brain damage is an important factor contributing to mortality or lasting neurological sequelae in CNS infections, such as cryptococcal meningoencephalitis (CM), but little is known about natural immunoregulatory mechanisms in the infected brain. Here we report that regulatory T cells (Tregs) are a central immunoregulatory component in CM. Tregs are present within the CNS in both human CM patients and in the experimental murine CM. Treg-depletion exacerbates Th1-driven brain inflammation and neurological symptoms, accelerating mortality, despite enhanced fungal clearance in mouse CM. Aligned brain NanoString, scRNA-seq, and flow cytometry analyses revealed that Tregs reduce brain inflammation, especially T-cell recruitment activation and differentiation, shielding the brain fro

SUBMITTER: Li H 

PROVIDER: S-EPMC12324597 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature