Aryl hydrocarbon receptor and Krüppel like factor 10 mediate a transcriptional axis modulating immune homeostasis in mosquitoes
Immune responses require delicate controls to maintain homeostasis while executing effective defense. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor. The Krüppel-like factor 10 (KLF10) is a C2H2 zinc-finger containing transcription factor. The functions of mosquito AhR an...
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Published in | Scientific reports Vol. 12; no. 1; p. 6005 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
09.04.2022
Nature Publishing Group Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | Immune responses require delicate controls to maintain homeostasis while executing effective defense. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor. The Krüppel-like factor 10 (KLF10) is a C2H2 zinc-finger containing transcription factor. The functions of mosquito AhR and KLF10 have not been characterized. Here we show that AhR and KLF10 constitute a transcriptional axis to modulate immune responses in mosquito
Anopheles gambiae
. The manipulation of AhR activities via agonists or antagonists repressed or enhanced the mosquito antibacterial immunity, respectively. KLF10 was recognized as one of the AhR target genes in the context. Phenotypically, silencing
KLF10
reversed the immune suppression caused by the AhR agonist. The transcriptome comparison revealed that silencing
AhR
and
KLF10
plus challenge altered the expression of 2245 genes in the same way. The results suggest that KLF10 is downstream of AhR in a transcriptional network responsible for immunomodulation. This AhR–KLF10 axis regulates a set of genes involved in metabolism and circadian rhythms in the context. The axis was required to suppress the adverse effect caused by the overactivation of the immune pathway IMD via the inhibitor gene
Caspar
silencing without a bacterial challenge
.
These results demonstrate that the AhR–KLF10 axis mediates an immunoregulatory transcriptional network as a negative loop to maintain immune homeostasis. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-022-09817-2 |