| First Author | Egarnes B | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 10 | Pages | e0186639 |
| PubMed ID | 29053748 | Mgi Jnum | J:248204 |
| Mgi Id | MGI:5917081 | Doi | 10.1371/journal.pone.0186639 |
| Citation | Egarnes B, et al. (2017) Treatment with the NR4A1 agonist cytosporone B controls influenza virus infection and improves pulmonary function in infected mice. PLoS One 12(10):e0186639 |
| abstractText | The transcription factor NR4A1 has emerged as a pivotal regulator of the inflammatory response and immune homeostasis. Although contribution of NR4A1 in the innate immune response has been demonstrated, its role in host defense against viral infection remains to be investigated. In the present study, we show that administration of cytosporone B (Csn-B), a specific agonist of NR4A1, to mice infected with influenza virus (IAV) reduces lung viral loads and improves pulmonary function. Our results demonstrate that administration of Csn-B to naive mice leads to a modest production of type 1 IFN. However, in IAV-infected mice, such production of IFNs is markedly increased following treatment with Csn-B. Our study also reveals that alveolar macrophages (AMs) appear to have a significant role in Csn-B effects, since selective depletion of AMs with clodronate liposome correlates with a marked reduction of IFN production, viral clearance and morbidity in IAV-infected mice. Furthermore, when reemergence of AMs is observed following clodronate liposome administration, an increased production of IFNs was detected in bronchoalveolar fluids of IAV-infected mice treated with Csn-B, supporting the contribution of AMs in Csn-B effects. While treatment of mice with Csn-B induces phosphorylation of transcriptional factors IRF3 and IRF7, the latter appears to be less indispensable since effects of Csn-B treatment on the synthesis of IFNs were slightly affected in IAV-infected mice lacking functional IRF7. Together, our results highlight the capacity of Csn-B and consequently of NR4A1 transcription factor in controlling IAV infection. |
