Effects of Aspergillus fumigatus gliotoxin and methylprednisolone on human neutrophils: implications for the pathogenesis of invasive aspergillosis

Aspergillus fumigatus (AF) is a ubiquitous mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. In stem cell transplant recipients, IA now occurs most frequently in the setting of therapy with corticosteroids, including methylprednisolone (MP). We showed previ...

Full description

Saved in:
Bibliographic Details
Published in:Journal of leukocyte biology 2007-10, Vol.82 (4), p.839-848
Main Authors: Orciuolo, Enrico, Stanzani, Marta, Canestraro, Martina, Galimberti, Sara, Carulli, Giovanni, Lewis, Russell, Petrini, Mario, Komanduri, Krishna V.
Format: Article
Language:English
Subjects:
Anti-Inflammatory Agents - adverse effects
Anti-Inflammatory Agents - pharmacology
Anti-Inflammatory Agents - therapeutic use
Apoptosis - drug effects
Apoptosis - immunology
Aspergillosis - drug therapy
Aspergillosis - immunology
Aspergillus fumigatus
Aspergillus fumigatus - immunology
Aspergillus fumigatus - pathogenicity
Cell Degranulation - drug effects
Cell Degranulation - immunology
Cells, Cultured
Dendritic Cells - immunology
Dendritic Cells - pathology
Gliotoxin - immunology
Gliotoxin - pharmacology
Humans
immune response
Immunocompromised Host - drug effects
Immunocompromised Host - immunology
Inflammation - chemically induced
Inflammation - immunology
Methylprednisolone - adverse effects
Methylprednisolone - pharmacology
Methylprednisolone - therapeutic use
micotoxin
Monocytes - immunology
Monocytes - pathology
Neutrophils - immunology
Neutrophils - pathology
Peroxidase - immunology
Phagocytosis - drug effects
Phagocytosis - immunology
polymorphonuclear leukocytes
Reactive Oxygen Species - immunology
Stem Cell Transplantation - adverse effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aspergillus fumigatus (AF) is a ubiquitous mold and the most common cause of invasive aspergillosis (IA) in immunocompromised patients. In stem cell transplant recipients, IA now occurs most frequently in the setting of therapy with corticosteroids, including methylprednisolone (MP). We showed previously that gliotoxin (GT), an AF‐derived mycotoxin, induces apoptosis in monocytes and dendritic cells, resulting in the suppression of AF‐specific T cell responses. We examined the ability of GT to induce apoptosis in polymorphonuclear leukocytes (PMN) and assessed GT effects on important neutrophil functions, including phagocytic function, degranulation, myeloperoxidase activity, and the production of reactive oxygen species (ROS). In contrast to its effects on monocytes, PMN remained resistant to GT‐mediated apoptosis. Although many essential neutrophil functions were unaffected, GT inhibited phagocytosis and also induced a decrease in ROS generation by PMN. In contrast, MP therapy potentiated ROS production, suggesting a mechanism that may facilitate tissue injury in IA. Distinct from its effects on untreated PMN, GT augmented ROS production in MP‐treated PMN. Our results suggest that although GT may suppress the adaptive immune response, GT may also serve to increase PMN‐mediated inflammation, which is likely to play an important role in tissue destruction in the setting of IA.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.0207090