Immunotherapeutic approaches in invasive Aspergillus infections



Invasive aspegillosis (IA) has become a major complication in immunocompromised patients. In addition to Aspergillus fumigatus, the most common cause of IA, other Aspergillus spp. can cause invasive infections with high mortality. Recent studies examining the immunopathogenesis of IA have provided increased insights into the relative importance of the different compartments of host immune defenses against Aspergillus spp. such as macrophages, neutrophils, T helper 1 and 2 as well as NK lymphocytes. In parallel, a number of immunoenhancing cytokines have been discovered and several studies of their involvement in antifungal host defenses both in vitro and in animal models of IA have been published. Due to their ability to upregulate phagocyte number and/or function, the cytokines of greatest interest are granulocyte colonystimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, interferon-g, interleukin-1 and tumor necrosis factor-a. Adjuvant use of these cytokines may be of value for IA, although a clinical benefit to patients is still limited to few studies and indications. In addition, reconstitution of immune response by transfusion of large numbers of allogeneic phagocytes previously stimulated with hemopoietic cytokines (i.e. G-CSF) has shown preliminary beneficial role on the management of refractory fungal infections including IA. Th2 cytokines, i.e. interleukin-4 and -10, have down-regulatory effects on antifungal phagocytic activity against A. fumigatus. Neutralization of these cytokines and their immunosuppressive function has beneficial effects on murine models of IA. The in vitro and in vivo demonstrations of improved outcome of IA by the regulation of these cytokines offer novel approaches in the management of this serious infection in immunocompromised patients. Further evaluation of safety and efficacy of these immunotherapeutic modalities is a new and promising area for research.

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11th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 11th (2001)