title: Calcineurin inhibitors impair neutrophil activity against Aspergillus fumigatus in allogeneic hematopoietic stem cell transplant recipients.
abstract: Neutrophils are key effectors against the widely distributed mold Aspergillus fumigatus, which is a major threat for immunocompromised patients, including allogeneic hematopoietic stem cell transplant (HSCT) recipients. Yet little is known about neutrophil activity over time after cell transplantation, especially regarding A fumigatus.
  
  
  
  We aimed at assessing the activity of neutrophils on A fumigatus in allogeneic HSCT recipients at different posttransplantation time points.
  
  
  
  We performed a longitudinal study involving 37 patients undergoing HSCT, drawing blood samples at engraftment and at 2, 6, and 10 months after the HSCT. Posttransplantation neutrophil activity in the recipients was compared with that of the respective donors. Neutrophil/A fumigatus coculture, flow cytometry, and video microscopy were used to assess neutrophil inhibition of fungal growth, cell/fungus interactions, reactive oxygen species production, major surface molecule expression, and neutrophil extracellular trap (NET) formation.
  
  
  
  The ability of neutrophils to interfere with Aspergillus species hyphal growth was impaired after HSCT. The administration of calcineurin inhibitors appeared to play an important role in this impairment. We also observed that post-HSCT neutrophils produced less NETs, which was correlated with increased fungal growth. Tapering immunosuppression led to the recuperation of inhibition capacity 10 months after HSCT.
  
  
  
  In HSCT recipients neutrophil-driven innate immunity to fungi is altered in the early posttransplantation period (between recovery from neutropenia and up to 6 months). This alteration is at least partly related to administration of calcineurin inhibitors and diminution of NETs production.
authors.affiliation: AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Imbert
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
authors.forename: Priscillia
authors.initials: P
authors.lastname: Bresler
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Boissonnas
authors.affiliation: AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, France.
authors.forename: Lauraine
authors.initials: L
authors.lastname: Gauthier
authors.affiliation: AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service d'Hématologie, Paris, France.
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Souchet
authors.affiliation: AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service d'Hématologie, Paris, France.
authors.forename: Madalina
authors.initials: M
authors.lastname: Uzunov
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France; AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service d'Hématologie, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Leblond
authors.affiliation: AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France; AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service d'Hématologie, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Nguyen
authors.affiliation: AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France. Electronic address: arnaud.fekkar@aphp.fr.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fekkar
mesh_terms: D000328:Adult; D000368:Aged; D001232:Aspergillus fumigatus / Q000254:growth & development*; D065095:Calcineurin Inhibitors / Q000494:pharmacology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
chemical_list: D065095:Calcineurin Inhibitors; D017382:Reactive Oxygen Species
keywords: Innate immunity; calcineurin inhibitor; immune reconstitution; invasive fungal infection; transplantation