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Cytokine Augmentation Reverses Transplant Recipient Neutrophil Dysfunction Against the Human Fungal Pathogen Candida
Nicolas Barros1, Natalie Alexander2, Adam Viens2
1Division of Infectious Diseases, Indiana University Health, Indianapolis, Indiana, USA.
Background:
Solid organ transplant (SOT) and stem cell transplant (SCT) recipients are at increased risk of invasive fungal disease despite normal neutrophil counts. Here, we measure neutrophil anti-Candida activity.
Methods:
Twenty-one SOT and 19 SCT recipients were enrolled 2-4 months posttransplant and compared to 23 healthy control patients (HC). Neutrophils were coincubated with Candida albicans, and percentage killing and swarming responses were measured.
Results:
Neutrophils from transplant patients had decreased fungicidal capacity compared to HC (42%, 43%, and 72% for SCT, SOT, and HC, respectively; SCT vs HC: P < .0001; SOT vs HC: P < .0001; SOT vs SCT: P = .8), including diminished ability to control hyphal growth (HC vs SOT: 0.1455 vs 0.3894, P ≤ .001; HC vs SCT: 0.1455 vs 0.6295, P ≤ .0001, respectively). Serum from SCT, but not SOT, recipients, inhibited the ability of HC neutrophils to control C. albicans (37%, 45%, and 55% for SCT, SOT, and HC, respectively). Neutrophils' control of hyphal growth was partially restored with granulocyte colony-stimulating factor or granulocyte macrophage colony-stimulating factor.
Conclusions:
Despite normal circulating numbers, our data suggest that neutrophils from SOT and SCT recipients mount dysfunctional responses against C. albicans. Intrinsic neutrophil changes and extrinsic serum factors may be responsible for the dysfunction, which is partially reversed with cytokine augmentation.
Insights
Neutrophils from transplant patients show reduced anti-fungal activity, increasing infection risk. Cytokine therapy can partially restore neutrophil function, improving outcomes for solid organ and stem cell transplant recipients.
Area of Science:
- Immunology
- Transplantation Medicine
- Infectious Diseases
Background:
- Solid organ transplant (SOT) and stem cell transplant (SCT) recipients face a heightened risk of invasive fungal disease.
- This increased susceptibility occurs even when neutrophil counts are within normal ranges.
Purpose of the Study:
- To investigate neutrophil anti-Candida activity in SOT and SCT recipients.
- To compare the fungicidal capacity and hyphal growth control of neutrophils from transplant patients versus healthy controls.
Main Methods:
- Neutrophils from 21 SOT, 19 SCT recipients, and 23 healthy controls (HC) were coincubated with Candida albicans.
- Assessed were the percentage of fungal killing and neutrophil swarming responses.
- Serum inhibitory effects and the impact of cytokine augmentation (G-CSF, GM-CSF) were evaluated.
Main Results:
- Neutrophils from both SOT and SCT recipients exhibited significantly decreased fungicidal capacity compared to HC.
- Transplant recipients' neutrophils showed diminished ability to control Candida hyphal growth.
- Serum from SCT recipients, but not SOT recipients, inhibited healthy neutrophil anti-Candida activity.
- Granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) partially restored neutrophil function.
Conclusions:
- Neutrophils from SOT and SCT recipients display impaired anti-Candida responses despite normal counts.
- Both intrinsic neutrophil defects and extrinsic serum factors contribute to this dysfunction.
- Cytokine therapy offers a potential strategy to partially reverse neutrophil dysfunction in transplant patients.
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