Calcineurin inhibitors impair neutrophil activity against Aspergillus fumigatus in allogenic hematopoietic stem cell transplant recipients

Publication date: Available online 7 April 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Sébastien Imbert, Priscillia Bresler, Alexandre Boissonnas, Lauraine Gauthier, Laëtitia Souchet, Madalina Uzunov, Véronique Leblond, Dominique Mazier, Stéphanie Nguyen, Arnaud Fekkar
BackgroundNeutrophils are key effectors against the widely distributed mold Aspergillus fumigatus, which is a major threat for immunocompromised patients including allogenic hematopoietic stem cell transplant (HSCT) recipients. Yet little is known about neutrophil activity over time after cell transplantation, especially regarding A. fumigatus.ObjectiveWe aimed at assessing the activity of neutrophils on A. fumigatus in allogenic HSCT recipients at different post-transplant time points.MethodsWe performed a longitudinal study involving 37 HSCT patients, drawing blood samples at engraftment and at two, six and ten months after the HSCT. Post-transplant neutrophil activity in the recipients was compared to that of the respective donors. Neutrophil/ Aspergillus co-culture, 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 traps (NETs) formation.ResultsThe ability of neutrophils to interfere with Aspergillus 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 post-HSCT.ConclusionIn HSCT recipients, neutrophil-driven innate immunity to fungi is altered in the early post-transplant period (between recovery from neutropenia and up to 6 months). This alteration is at least partly related to the administration of calcineurin inhibitors and the diminution of NETs production.

Teaser

In allogenic hematopoietic stem cell transplant recipients, fungal innate immunity driven by neutrophils is altered during the first months of the graft, in relation with the use of calcineurin inhibitors.


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