| First Author | Liu B | Year | 2016 |
| Journal | Sci Signal | Volume | 9 |
| Issue | 436 | Pages | ra70 |
| PubMed ID | 27405980 | Mgi Jnum | J:260301 |
| Mgi Id | MGI:6141813 | Doi | 10.1126/scisignal.aac9340 |
| Citation | Liu B, et al. (2016) Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways. Sci Signal 9(436):ra70 |
| abstractText | Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate the innate immune response through the production of cytokines. The innate immune response depends on the timing of encountering PAMPs, suggesting a short-term "memory." In particular, activation of TLR3 appears to prime macrophages for the subsequent activation of TLR7, which leads to synergistically increased production of cytokines. By developing a calibrated mathematical model for the kinetics of TLR3 and TLR7 pathway crosstalk and providing experimental validation, we demonstrated the involvement of the Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in controlling the synergistic production of cytokines. Signaling through this pathway played a dual role: It mediated the synergistic production of cytokines, thus boosting the immune response, and it also maintained homeostasis to avoid an excessive inflammatory response. Thus, we propose that the JAK-STAT pathway provides a cytokine rheostat mechanism, which enables macrophages to fine-tune their responses to multiple, temporally separated infection events involving the TLR3 and TLR7 pathways. |
