Immune Correlates of Protection in Human Invasive Aspergillosis

Abstract

An improved understanding of the pathogenesis of Aspergillus infections has facilitated the identification of host biomarkers that, if validated in well-designed prospective studies, could facilitate clinical decision making in the treatment and prophylaxis of invasive aspergillosis in immunocompromised individuals. Protective immunity against Aspergillus depends on a highly coordinated interaction between the innate and adaptive arms of the immune system. Fungal recognition via pattern recognition receptors, such as pentraxin 3, dectin-1, and Toll-like receptors, leads to complement activation, phagocytosis, and killing of ingested fungi. Aspergillus-specific T-helper 1 and 17 cells produce cytokines such as interferon γ and interleukin 17, which facilitate macrophage activation and neutrophil recruitment, respectively. Genetic (or drug-induced) defects in components of these networks of antifungal immunity result in increased risk of invasive aspergillosis after chemotherapy or transplantation. We review the most important genetic, immunological, and pharmacological factors that influence human susceptibility to Aspergillus and discuss the potential role of immune biomarkers in risk stratification strategies that facilitate individualized antifungal therapy/prophylaxis in immunocompromised hosts.