Nicolas Barros1, Natalie Alexander2, Adam Viens2, Kyle Timmer2, Natalie Atallah2,3,4, Sally A I Knooihuizen3, Alex Hopke4,5,6, Allison Scherer2,3,4, Zeina Dagher2,3,4, Daniel Irimia4,5,6, Michael K Mansour2,3,4. 1. Division of Infectious Diseases, Indiana University Health, Indianapolis, Indiana, USA. 2. Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA. 3. Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. 4. Harvard Medical School, Boston, Massachusetts, USA. 5. Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA. 6. Shriners Burns Hospital, Boston, Massachusetts, USA.
Abstract
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.
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.
Authors: D Neofytos; J A Fishman; D Horn; E Anaissie; C-H Chang; A Olyaei; M Pfaller; W J Steinbach; K M Webster; K A Marr Journal: Transpl Infect Dis Date: 2010-01-25 Impact factor: 2.228
Authors: J Gavaldà; Y Meije; J Fortún; E Roilides; F Saliba; O Lortholary; P Muñoz; P Grossi; M Cuenca-Estrella Journal: Clin Microbiol Infect Date: 2014-09 Impact factor: 8.067
Authors: Natalie J Alexander; David J Bozym; Joceyln R Farmer; Priscilla Parris; Adam Viens; Natalie Atallah; Alex Hopke; Allison Scherer; Zeina Dagher; Nicolas Barros; Sally A I Knooihuizen; Rebecca R Saff; Mark S Pasternack; Ryan W Thompson; Daniel Irimia; Michael K Mansour Journal: J Allergy Clin Immunol Pract Date: 2020-08-24
Authors: S J van Hal; D J E Marriott; S C A Chen; Q Nguyen; T C Sorrell; D H Ellis; M A Slavin Journal: Transpl Infect Dis Date: 2009-04-07 Impact factor: 2.228
Authors: Adam L Viens; Kyle D Timmer; Natalie J Alexander; Rana Barghout; Jelena Milosevic; Alex Hopke; Natalie J Atallah; Allison K Scherer; David B Sykes; Daniel Irimia; Michael K Mansour Journal: J Immunol Date: 2022-03-11 Impact factor: 5.422
Authors: Alex Hopke; Tian Lin; Allison K Scherer; Ashley E Shay; Kyle D Timmer; Brittany Wilson-Mifsud; Michael K Mansour; Charles N Serhan; Daniel Irimia; Bryan P Hurley Journal: iScience Date: 2022-09-28