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Updated: Apr 19, 2026
Live Imaging of Antifungal Activity by Human Primary Neutrophils and Monocytes in Response to A. fumigatus
Published on: April 19, 2017
A second stimulus required for enhanced antifungal activity of human neutrophils in blood is provided by
Kerstin Hünniger1, Kristin Bieber1, Ronny Martin1
1Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute, 07745 Jena, Germany;
Abstract:
Polymorphonuclear neutrophilic granulocytes (PMN) as cellular components of innate immunity play a crucial role in the defense against systemic Candida albicans infection. To analyze stimuli that are required for PMN activity during C. albicans infection in a situation similar to in vivo, we used a human whole-blood infection model. In this model, PMN activation 10 min after C. albicans infection was largely dependent on the anaphylatoxin C5a. Most importantly, C5a enabled blood PMN to overcome filament-restricted recognition of C. albicans and allowed efficient elimination of nonfilamentous C. albicans cph1Δ/efg1Δ from blood. Major PMN effector mechanisms, including oxidative burst, release of secondary granule contents and initial fungal phagocytosis could be prevented by blocking C5a receptor signaling. Identical effects were achieved using a humanized Ab specifically targeting human C5a. Phagocytosis of C. albicans 10 min postinfection was mediated by C5a-dependent enhancement of CD11b surface expression on PMN, thus establishing the C5a-C5aR-CD11b axis as a major modulator of early anti-Candida immune responses in human blood. In contrast, phagocytosis of C. albicans by PMN 60 min postinfection occurred almost independently of C5a and mainly contributed to activation of phagocytically active PMN at later time points. Our results show that C5a is a critical mediator in human blood during C. albicans infection.
Insights
The anaphylatoxin C5a is crucial for polymorphonuclear neutrophilic granulocytes (PMN) to effectively combat Candida albicans infections in human blood, enhancing early immune responses.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Polymorphonuclear neutrophilic granulocytes (PMN) are key innate immune cells fighting systemic Candida albicans infections.
- Understanding PMN activation during infection is vital for developing effective treatments.
Purpose of the Study:
- To investigate the stimuli required for PMN activation during Candida albicans infection in a human whole-blood model.
- To elucidate the role of anaphylatoxin C5a in early anti-Candida immune responses.
Main Methods:
- Utilized a human whole-blood infection model with Candida albicans.
- Analyzed PMN activation, oxidative burst, granule release, and phagocytosis.
- Investigated the effects of blocking C5a receptor signaling and using a humanized anti-C5a antibody.
- Assessed CD11b surface expression on PMN.
Main Results:
- PMN activation at 10 minutes post-Candida albicans infection was highly dependent on C5a.
- C5a facilitated PMN recognition and elimination of nonfilamentous C. albicans.
- Blocking C5a signaling or using anti-C5a antibodies inhibited major PMN effector functions.
- C5a-dependent CD11b expression mediated early C. albicans phagocytosis.
- Later phagocytosis (60 minutes) was largely C5a-independent.
Conclusions:
- C5a is a critical mediator of early innate immune responses against Candida albicans in human blood.
- The C5a-C5aR-CD11b axis significantly modulates early anti-Candida immunity.
- Targeting C5a may offer therapeutic potential for systemic Candida infections.
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