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. 2025 Jun 3;21(6):e1013185.
doi: 10.1371/journal.ppat.1013185. eCollection 2025 Jun.

Roles of TLR9: Gatekeeper to fungal infections

Elias Barbosa da Silva-Junior  1 , Leonardo Freire-de-Lima  1 , Luciana Polaco Covre  1   2 , Alexandre Morrot  3   4 , Herbert Leonel de Matos Guedes  4   5 , Debora Decote-Ricardo  6 , Celio Geraldo Freire-de-Lima  1
Affiliations

Roles of TLR9: Gatekeeper to fungal infections

Elias Barbosa da Silva-Junior et al. PLoS Pathog. .
No abstract available

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. The dual role of TLR9 in Candida albicans infection.
The role of TLR9 in the inflammatory response to C. albicans infection remains controversial. (A) Some studies suggest that TLR9 activation modulates the antifungal immune response by inhibiting TNF-α production, which may favor C. albicans intracellular survival. (B) Conversely, TLR9 activation induces IL-12 production by monocytes, promoting a protective Th1 antifungal response. Additionally, both endosomal TLR9 (eTLR9) and surface-expressed TLR9 (sTLR9) can recognize C. albicans DNA, contributing to neutrophil extracellular trap (NET) release for biofilm control. Both panels were created in BioRender. da Silva-Junior, E. (2025) https://BioRender.com/0nlnhoe.
Fig 2
Fig 2. The role of TLR9 during epithelial-CNS barrier disruption by Cryptococcus spp.
Cryptococcal yeasts can cross the blood–brain barrier (BBB) and blood-retinal barrier (BRB) by “Trojan horse” mechanism (a), paracellular pathway (b), and cellular traversal (c). Cryptococcus crosses the epithelial-CNS barrier after being carried by phagocytes that transmigrate to the brain, releasing the yeasts after exocytosis (lytic and non-lytic). Microglia can phagocyte cryptococcal yeasts and the TLR9-mediated antifungal immune response, characterized by TNF-α and IL-6 secretion. Chemotactic molecules CXCL1 and CXCL2 are secreted after TLR9 activation and promote monocytes and neutrophil recruitment, leading to a local inflammatory response. TLR9: Toll-like receptor 9; GS: Glutamine Synthetase; TNF-α: Tumor Necrosis Factor-α; CXCL: Chemokine (C-X-C) motif ligand; IL: Interleukin. Created in BioRender. da Silva-Junior, E. (2025) https://BioRender.com/4tapt8q.
See this image and copyright information in PMC

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