Th17 cells in the setting of Aspergillus infection and pathology.
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-inflammatory 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.
Zelante
Teresa
T
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy. metzelante@hotmail.com
Bozza
Silvia
S
De Luca
Antonella
A
D'Angelo
Carmen
C
Bonifazi
Pierluigi
P
Moretti
Silvia
S
Giovannini
Gloria
G
Bistoni
Francesco
F
Romani
Luigina
L
D000818:Animals; D001228:Aspergillosis / Q000276:immunology* / Q000473:pathology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D053760:Interleukin-23 Subunit p19 / Q000276:immunology; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19