Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity.
Both interferon-gamma-producing type 1 T helper (Th1)- and interleukin-17 (IL-17)-producing Th17 cells have been proposed to be involved in anti-fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the relative importance of the Th1 versus Th17 cellular immune pathways for the human anti-Aspergillus host defence. Using human peripheral blood mononuclear cells and a system consisting of monocyte-derived macrophages with lymphocytes, we found that Aspergillus fumigatus is a weak inducer of human IL-17 but induces a strong Th1 response. These data were validated by the very low IL-17 levels in bronchoalveolar lavage fluid and serum of patients with invasive aspergillosis. Surprisingly, live A. fumigatus reduced IL-17 production induced by mitogenic stimuli. This effect was mediated through the propensity of A. fumigatus to metabolize tryptophan and release kynurenine, which modulates the inflammatory response through inhibition of IL-17 production. In conclusion, A. fumigatus does not stimulate production of IL-17 and human host defence against aspergillosis may not rely on potent Th17 responses.
Chai
Louis Y A
LY
Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
van de Veerdonk
Frank
F
Marijnissen
Renoud J
RJ
Cheng
Shih-Chin
SC
Khoo
Ai Leng
AL
Hectors
Magda
M
Lagrou
Katrien
K
Vonk
Alieke G
AG
Maertens
Johan
J
Joosten
Leo A B
LA
Kullberg
Bart-Jan
BJ
Netea
Mihai G
MG
D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D020381:Interleukin-17