Abstract
IL-1 drives Th responses, particularly Th17, in host defense. Sharing the same co-receptor, the IL-1 family member IL-36 exhibits properties similar to those of IL-1. In the present study, we investigated the role of IL-36 in Aspergillus fumigatus-induced human Th responses. We observed that different morphological forms of A. fumigatus variably increase steady-state mRNA of IL-36 subfamily members. IL-36α is not significantly induced by any morphological form of Aspergillus. Most strikingly, IL-36γ is significantly induced by live A. fumigatus conidia and heat-killed hyphae, whereas IL-36Ra (IL-36 receptor antagonist) is significantly induced by heat-killed conidia, hyphae, and live conidia. We also observed that IL-36γ expression is dependent on the dectin-1/Syk and TLR4 signaling pathway. In contrast, TLR2 and CR3 inhibit IL-36γ expression. The biological relevance of IL-36 induction by Aspergillus is demonstrated by experiments showing that inhibition of the IL-36 receptor by IL-36Ra reduces Aspergillus-induced IL-17 and IFN-γ. These data describe that IL-36-dependent signals are a novel cytokine pathway that regulates Th responses induced by A. fumigatus, and demonstrate a role for TLR4 and dectin-1 in the induction of IL-36γ.
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aspergillosis / genetics
-
Aspergillosis / immunology*
-
Aspergillosis / metabolism
-
Aspergillosis / microbiology
-
Aspergillus fumigatus / immunology*
-
Forkhead Transcription Factors / genetics
-
Forkhead Transcription Factors / immunology
-
Forkhead Transcription Factors / metabolism
-
Humans
-
Hyphae / immunology
-
Interferon-gamma / genetics
-
Interferon-gamma / immunology
-
Interferon-gamma / metabolism
-
Interleukin-17 / genetics
-
Interleukin-17 / immunology
-
Interleukin-17 / metabolism
-
Lectins, C-Type / genetics
-
Lectins, C-Type / immunology
-
Lectins, C-Type / metabolism
-
Macrophage-1 Antigen / genetics
-
Macrophage-1 Antigen / immunology
-
Macrophage-1 Antigen / metabolism
-
RNA, Messenger / genetics
-
Receptors, Interleukin / genetics
-
Receptors, Interleukin / immunology*
-
Receptors, Interleukin / metabolism
-
Signal Transduction / genetics
-
Signal Transduction / immunology
-
Spores, Fungal / immunology
-
Th1 Cells / immunology*
-
Th1 Cells / metabolism
-
Th17 Cells / immunology*
-
Th17 Cells / metabolism
-
Toll-Like Receptor 2 / genetics
-
Toll-Like Receptor 2 / immunology
-
Toll-Like Receptor 2 / metabolism
-
Toll-Like Receptor 4 / genetics
-
Toll-Like Receptor 4 / immunology
-
Toll-Like Receptor 4 / metabolism
Substances
-
CLEC7A protein, human
-
FOXP3 protein, human
-
Forkhead Transcription Factors
-
Interleukin-17
-
Lectins, C-Type
-
Macrophage-1 Antigen
-
RNA, Messenger
-
Receptors, Interleukin
-
TLR2 protein, human
-
TLR4 protein, human
-
Toll-Like Receptor 2
-
Toll-Like Receptor 4
-
interleukin-36 receptor, human
-
Interferon-gamma