Foxp3+ Regulatory T Cells Restrain Th1 Response Shielding the Brain from Lethal Inflammatory Damage during Cryptococcal Meningoencephalitis
Hailong Li, Rylan Hissong, Kristie D. Goughenour, Yekateryna Sinitsyna, Maia Lintner, Brian Song, Heineken Q. Daguplo, Clifford S Cho, Anutosh Ganguly, Grace Y. Chen, Jessica C. Hargarten, Peter R. Williamson, Jintao Xu, Michal A. Olszewski
TL;DR
Regulatory T cells protect the brain from inflammation during fungal meningitis by reducing harmful immune responses and promoting repair.
Contribution
The study identifies Tregs as key protectors in the brain during cryptococcal meningitis, revealing their recruitment mechanism and therapeutic potential.
Findings
Tregs reduce brain inflammation and shield the brain from neurological damage in cryptococcal meningitis.
CCR8-mediated recruitment and IL-10 production by Tregs are critical for their protective role.
Treg-enhancing therapy improves survival and neurological outcomes in mice with meningitis.
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 from neurological damage. The major CNS-Treg recruitment appears to be chemokine receptor…
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Taxonomy
TopicsFungal Infections and Studies · Antifungal resistance and susceptibility · Cytomegalovirus and herpesvirus research