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Mechanisms of Talaromyces marneffei induced CNS injury: Synergistic roles of tauopathy, pyroptosis, and microglial inflammation

Summary

A dangerous fungus called Talaromyces marneffei can invade the brain and cause serious damage in people with weakened immune systems. The study shows the fungus harms brain cells through two pathways: direct damage to neurons and indirect damage through activation of brain immune cells that release harmful inflammatory chemicals. Understanding these mechanisms could help develop better treatments for this life-threatening infection.

Background

Talaromyces marneffei is an opportunistic dimorphic fungus that causes systemic mycosis, particularly in immunocompromised individuals. Recent clinical reports suggest potential CNS involvement, but the neuroinvasive mechanisms remain poorly understood. This study investigates whether T. marneffei can invade the brain parenchyma and establish the underlying pathogenic mechanisms.

Objective

To determine if T. marneffei can invade the central nervous system and identify the molecular mechanisms of CNS damage through both in vivo mouse models and in vitro cell culture systems.

Results

T. marneffei successfully invaded hippocampal and cortical tissues, impairing learning, memory, and motor balance in infected mice. Transcriptomic analysis revealed activation of neurodegeneration pathways. Elevated expression of Tau46, GSDMD, and Caspase-1 indicated involvement of tauopathy and pyroptosis. M1-polarized microglia released pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) contributing to indirect neuronal damage.

Conclusion

T. marneffei induces CNS injury through dual mechanisms: direct neuronal damage via Tau pathology and GSDMD-dependent pyroptosis, and indirect inflammation-mediated injury via M1-polarized microglial activation. These findings provide potential therapeutic targets for fungal CNS infections in immunocompromised populations.
  • Published in:Virulence,
  • Study Type:Experimental Research,
  • Source: PMID: 41146459
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