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Cytosolic receptors and signaling in antifungal immunity

Sandra Khau1,2, Guillaume Desoubeaux1,2,3, Mustapha Si-Tahar1,2

  • 1Inserm, U1100, Centre d'Étude des Pathologies Respiratoires, Tours, France.

The EMBO Journal
|November 17, 2025
PubMed

Insights

The innate immune system uses pattern-recognition receptors (PRRs) to detect fungi. This review focuses on cytosolic receptors and signaling pathways crucial for antifungal immunity.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • The host innate immune system is the primary defense against fungal infections.
  • Pattern-recognition receptors (PRRs) are essential for recognizing fungal pathogens via pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs).
  • PRRs are located on the cell surface, in endosomes, or in the cytosol, initiating distinct signaling pathways.

Purpose of the Study:

  • To review the role of cytosolic receptors in sensing fungi.
  • To summarize the signaling pathways activated by these cytosolic receptors in antifungal innate immunity.

Main Methods:

  • Literature review of scientific publications on innate immunity and fungal recognition.
  • Analysis of known PRR families, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), Nod-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs).

Main Results:

  • Membrane-bound TLRs and CLRs are key for initial fungal recognition.
  • Cytosolic sensors (NLRs, ALRs, RLRs) detect fungal elements that escape cellular compartments.
  • Activation of these receptors triggers specific signaling cascades essential for antifungal host protection.

Conclusions:

  • Cytosolic PRRs play a critical role in detecting intracellular fungal pathogens.
  • Understanding these cytosolic sensing mechanisms and pathways is vital for developing effective antifungal strategies.
Keywords:
Cell DeathCytosolic SensorsFungiInflammasomeInterferon

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