| First Author | Lee S | Year | 2018 |
| Journal | Front Immunol | Volume | 9 |
| Pages | 1954 | PubMed ID | 30214444 |
| Mgi Jnum | J:311858 | Mgi Id | MGI:6780975 |
| Doi | 10.3389/fimmu.2018.01954 | Citation | Lee S, et al. (2018) ATF3 Stimulates IL-17A by Regulating Intracellular Ca(2+)/ROS-Dependent IL-1beta Activation During Streptococcus pneumoniae Infection. Front Immunol 9:1954 |
| abstractText | Activating transcription factor-3 (ATF3) in the ER stress pathway induces cytokine production and promotes survival during gram-positive bacterial infection. IL-17A is a critical cytokine that is essential for clearance of Streptococcus pneumoniae. However, the mechanism by which ATF3 induces IL-17A production remains unknown. Here, we show that ATF3 induces IL-17A production via NLRP3 inflammasome-dependent IL-1beta secretion. Survival rates were comparable in IL-17A-depleted and ATF3 KO mice but were lower than in WT mice treated with isotype control, indicating that ATF3 positively regulated IL-17A production. Indeed, ATF3 KO mice showed a marked reduction in IL-17A protein and mRNA expression compared to levels in WT mice. Moreover, mitochondrial IL-1beta production by bone marrow-derived macrophages was significantly reduced in ATF3 KO mice as a result of the disruption of cellular ROS and Ca(2+) homeostasis. Accordingly, ATF3 KO mice displayed diminished survival and bacterial clearance following S. pneumoniae infection. Taken together, these data suggest a mechanism in which macrophage ATF3 promotes IL-17A production in gammadelta T cells to rapidly induce host defenses during early S. pneumoniae infection. |
