DnaJ-induced TLR7 mediates an increase in interferons through the TLR4-engaged AKT/NF-κB and JNK signaling pathways in macrophages

Toll-like receptor 7 (TLR7) signaling plays pivotal roles in innate immunity by sensing viral single-stranded RNA thereby triggering inflammatory signaling cascades and eliciting protective antiviral responses. In this study, we found that TLR7 expression is highly induced in response to Pseudomonas...

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Bibliographic Details
Published in:Microbial pathogenesis 2022-04, Vol.165, p.105465-105465, Article 105465
Main Authors: Yu, Hyeonseung, Huh, Jin-Won, Bai, Fang, Ha, Un-Hwan
Format: Article
Language:English
Subjects:
Antiviral Agents
DnaJ
IFN
Interferons - metabolism
Macrophages - metabolism
MAP Kinase Signaling System
NF-kappa B - metabolism
Proto-Oncogene Proteins c-akt - metabolism
Pseudomonas aeruginosa
Pseudomonas aeruginosa - metabolism
TLR7
Toll-Like Receptor 4 - genetics
Toll-Like Receptor 4 - metabolism
Toll-Like Receptor 7 - genetics
Toll-Like Receptor 7 - metabolism
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Summary:Toll-like receptor 7 (TLR7) signaling plays pivotal roles in innate immunity by sensing viral single-stranded RNA thereby triggering inflammatory signaling cascades and eliciting protective antiviral responses. In this study, we found that TLR7 expression is highly induced in response to Pseudomonas aeruginosa (P. aeruginosa) infection in a dose- and time-dependent manner. P. aeruginosa-derived DnaJ, a homolog of HSP40, was identified as a related inducing agent for TLR7 expression, and expression of DnaJ was stimulated when host cells were infected with P. aeruginosa. Interestingly, DnaJ was not involved in mediating an increase in the expression levels of TLR3 and TLR8, other well-known antiviral receptors. The induction of TLR7 in response to DnaJ was mediated by the activation of the AKT (Thr308 and Ser473)/NF-κB and p38/JNK MAPKs signaling pathways, consequently transmitting related signals for the expression of interferons (IFNs). Of note, these antiviral responses were regulated, at least in part, by TLR4, which senses the presence of DnaJ and then promotes downstream activation of the AKT (Ser473)/NF-κB and JNK signaling cascades. Taken together, these results suggest that P. aeruginosa-derived DnaJ is sufficient to promote an increase in TLR7 expression in the TLR4-engaged AKT/NF-κB and JNK signaling pathways, thereby promoting an increased antiviral response through the elevated expression of IFNs. •TLR7 senses viral ssRNA thereby eliciting protective antiviral responses.•DnaJ, HSP40 homolog, is sufficient to promote an increase in TLR7 expression.•The induction is mediated by TLR4-engaged AKT/NF-κB and JNK pathways.
ISSN:0882-4010
1096-1208
DOI:10.1016/j.micpath.2022.105465