Sébastien Imbert1, Priscillia Bresler2, Alexandre Boissonnas2, Lauraine Gauthier1, Laëtitia Souchet3, Madalina Uzunov3, Véronique Leblond4, Dominique Mazier5, Stéphanie Nguyen4, Arnaud Fekkar6. 1. AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, France. 2. Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France. 3. AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service d'Hématologie, Paris, France. 4. 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. 5. 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. 6. 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.
Abstract
BACKGROUND: 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. OBJECTIVE: We aimed at assessing the activity of neutrophils on A fumigatus in allogeneic HSCT recipients at different posttransplantation time points. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. OBJECTIVE: We aimed at assessing the activity of neutrophils on A fumigatus in allogeneic HSCT recipients at different posttransplantation time points. METHODS: 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. RESULTS: 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. CONCLUSION: 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: Aaron D Mood; Ilandari Dewage Udara Anulal Premachandra; Stanley Hiew; Fuqiang Wang; Kevin A Scott; Nathan J Oldenhuis; Haoping Liu; David L Van Vranken Journal: ACS Med Chem Lett Date: 2017-01-11 Impact factor: 4.345
Authors: Tamara Hoppenbrouwers; Anouchska S A Autar; Andi R Sultan; Tsion E Abraham; Wiggert A van Cappellen; Adriaan B Houtsmuller; Willem J B van Wamel; Heleen M M van Beusekom; Johan W van Neck; Moniek P M de Maat Journal: PLoS One Date: 2017-05-09 Impact factor: 3.240