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Cytokine Augmentation Reverses Transplant Recipient Neutrophil Dysfunction against the human fungal pathogen, Candida albicans.

BACKGROUND
Solid organ (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 post-transplant and compared to 23 healthy control patients (HC). Neutrophils were co-incubated with C. albicans and percent killing, and swarming responses were measured.


RESULTS
Neutrophils from transplant patients had decreased fungicidal capacity compared to HC (42%, 43%, 72%; SCT, SOT, and HC respectively; SCT vs. HC p<0.0001, SOT vs. HC p<0.0001, SOT vs. SCT p=0.8) including diminished ability to control hyphal growth (HC vs SOT and HC vs. SCT, 0.1455 vs. 0.3894, p ≤0.001, 0.1455 vs. 0.6295, p ≤0.0001, respectively). Serum from SCT, but not SOT recipients, inhibited the ability of HC neutrophils to control C. albicans (37%, 45%, 55%; SCT, SOT, and HC, respectively). Neutrophils control of hyphal growth was partially restored with G-CSF or GM-CSF.


CONCLUSION
Despite normal circulating numbers, our data suggests 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.