| First Author | Vieira RS | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 775346 | PubMed ID | 35095849 |
| Mgi Jnum | J:319728 | Mgi Id | MGI:6864837 |
| Doi | 10.3389/fimmu.2021.775346 | Citation | Vieira RS, et al. (2021) STING Signaling Drives Production of Innate Cytokines, Generation of CD8(+) T Cells and Enhanced Protection Against Trypanosoma cruzi Infection. Front Immunol 12:775346 |
| abstractText | A variety of signaling pathways are involved in the induction of innate cytokines and CD8(+) T cells, which are major players in protection against acute Trypanosoma cruzi infection. Previous data have demonstrated that a TBK-1/IRF3-dependent signaling pathway promotes IFN-beta production in response to Trypanosoma cruzi, but the role for STING, a main interactor of these proteins, remained to be addressed. Here, we demonstrated that STING signaling is required for production of IFN-beta, IL-6, and IL-12 in response to Trypanosoma cruzi infection and that STING absence negatively impacts activation of IRF-dependent pathways in response to the parasite. We reported no significant activation of IRF-dependent pathways and cytokine expression in RAW264.7 macrophages in response to heat-killed trypomastigotes. In addition, we showed that STING is essential for T. cruzi DNA-mediated induction of IFN-beta, IL-6, and IL-12 gene expression in RAW264.7 macrophages. We demonstrated that STING-knockout mice have significantly higher parasitemia from days 5 to 8 of infection and higher heart parasitism at day 13 after infection. Although we observed similar heart inflammatory infiltrates at day 13 after infection, IFN-beta, IL-12, CXCL9, IFN-gamma, and perforin gene expression were lower in the absence of STING. We also showed an inverse correlation between parasite DNA and the expression of CXCL9, IFN-gamma, and perforin genes in the hearts of infected animals at day 13 after infection. Finally, we reported that STING signaling is required for splenic IFN-beta and IL-6 expression early after infection and that STING deficiency results in lower numbers of splenic parasite-specific IFN-gamma and IFN-gamma/perforin-producing CD8(+) T cells, indicating a pivotal role for STING signaling in immunity to Trypanosoma cruzi. |
