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Updated: Jul 29, 2025

Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy
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C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection

Jigar V Desai1, Dhaneshwar Kumar2, Tilo Freiwald3

  • 1Fungal Pathogenesis Section, Laboratory of Clinical Immunology & Microbiology, National Institute of Allergy & Infectious Diseases, NIH, Bethesda, MD, USA.

Cell
|May 23, 2023
PubMed

Insights

The complement system

Area of Science:

  • Immunology
  • Mycology
  • Infectious Diseases

Background:

  • Systemic candidiasis is a frequent, lethal hospital-acquired infection.
  • It is an emerging complication of anti-complement C5 monoclonal antibody therapy.
  • This highlights a crucial role for C5 in antifungal immunity.

Purpose of the Study:

  • To investigate the role of the complement system in systemic candidiasis.
  • To identify biomarkers predictive of candidemia.
  • To elucidate the mechanisms of C5-mediated antifungal protection.

Main Methods:

  • Analysis of gene expression in candidemic patients.
  • Utilizing a mouse model of systemic candidiasis.
  • Investigating the impact of C5a receptor 1 (C5ar1) ablation on host response and survival.

Main Results:

  • Complement system gene transcription was the top induced pathway in candidemic patients and predicted candidemia.
  • C5a-C5aR1 signaling promoted fungal clearance and host survival via phagocyte function and tissue survival pathways (ERK, AKT).
  • C5ar1 deficiency altered macrophage metabolism, induced apoptosis, and increased mortality due to kidney injury.

Conclusions:

  • Local, phagocyte-derived C5 is essential for optimal phagocyte antimicrobial function.
  • C5 production by phagocytes confers innate protection against systemic fungal infections.
  • Reduced C5a levels or C5 polymorphisms affecting leukocyte C5 expression correlate with adverse patient outcomes.
Keywords:
C5C5aR1Candidaavacopancandidemiacandidiasiscomplementeculizumabkidney

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