Th17 cells in the setting ofAspergillusinfection and pathology

Abstract

Th17 cells in the setting of Aspergillus infection and pathology TERESA ZELANTE, SILVIA BOZZA, ANTONELLA DE LUCA, CARMEN D’ANGELO, PIERLUIGI BONIFAZI, SILVIA MORETTI, GLORIA GIOVANNINI, FRANCESCO BISTONI & LUIGINA ROMANI Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy Innate and adaptive immune responses act to generate the most effective form of immunity for protection against Aspergillus fumigatus. The decision of how to respond is still primarily determined by interactions between fungi and cells of the innate immune system, but the actions of T cells will feed back into this dynamic equilibrium to regulate the balance between pro-inflammatory and anti-inflam- matory signals. The enzyme indoleamine 2,3-dioxygenase, and tryptophan metabolites, acting as a bridge between dendritic cells and regulatory T cells, pivotally contribute to such a homeostatic condition by taming inflammatory responses. IL-23 and the newly described Th17 pathway, by means of negative regulation of tryptophan catabolism, play an inflammatory role previously attributed to uncontrolled Th1 response. Our data support a model in which IL- 23/IL-17A/Th17-driven inflammation promotes infection and impairs antifungal immune resistance. Thus, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to Aspergillus. Keywords inflammation, Aspergillus, indoleamine 2,3-dioxygenase, Th17 cells, regulatory T cells Introduction Invasive infections caused by Aspergillus moulds have increased in frequency during the last two decades and are associated with high rates of morbidity and mortality, especially among immunocompromised pa- tients [1,2]. Although immunocompetent and non- atopic subjects are relatively resistant to Aspergillus infections and diseases, A. fumigatus is associated with a spectrum of diseases in humans that include sapro- phytic colonization of pre-existing cavities (aspergil- loma

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