Anti-Aspergillus Human Host Defence Relies on Type 1 T Helper (Th1), Rather Than Type 17 T Helper (Th17), Cellular Immunity

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2009 Dec 17

PMID 20002791

Citations 59

Authors

Louis Y A Chai

Frank van de Veerdonk

Renoud J Marijnissen

Shih-Chin Cheng

Ai Leng Khoo

Magda Hectors

Katrien Lagrou

Alieke G Vonk

Johan Maertens

Leo A B Joosten

Bart-Jan Kullberg

Mihai G Netea

Affiliations

Soon will be listed here.

Abstract

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.

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