Abstract

When functioning properly, the immune system recognizes inhaled fungi and controls their growth, while avoiding injurious inflammation and allergy. 'Aspergillosis' represents a spectrum of clinical diseases resulting from impaired or excessive immune responses. Invasive aspergillosis is principally disease of severely immunocompromised patients, whereas allergic forms of aspergillosis result from an excessive inflammatory response to hyphae colonizing the sinopulmonary tract. We will review insights gained in host defense against Aspergillus species and the immunopathogenesis of Aspergillus-related diseases as well as important advances made in fungal diagnostics and antifungal therapy. Important advances have been made in diagnosis of invasive aspergillosis and in antifungal agents. Voriconazole was superior to amphotericin B deoxycholate as primary therapy for invasive aspergillosis. There is significant interest in combination antifungal therapy for invasive aspergillosis. Fungal genomics offers a powerful opportunity to gain knowledge about fungal virulence factors that can be targets for drug development. In addition, new insights have been gained regarding host defense against Aspergillus species that may be exploited therapeutically. We have gained substantial knowledge regarding how the immune system recognizes inhaled fungi and calibrates the inflammatory response. There has also been substantial progress in tools to diagnose aspergillosis and in antifungal therapeutics. Future progress will likely involve the development of more refined diagnostic tools, new classes of antifungal agents, and greater knowledge of pathogen and host factors that predispose to aspergillosis.

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