| Author | Pereira, Milton | |
| Author | Ramalho, Theresa | |
| Author | Andrade, Warrison A | |
| Author | Durso, Danielle F | |
| Author | Souza, Maria C | |
| Author | Fitzgerald, Katherine A | |
| Author | Golenbock, Douglas Taylor | |
| Author | Silverman, Neal | |
| Author | Gazzinelli, Ricardo Tostes | |
| Access date | 2024-04-01T12:52:56Z | |
| Available date | 2024-04-01T12:52:56Z | |
| Document date | 2024 | |
| Citation | PEREIRA, Milton et al. The IRAK1/IRF5 axis initiates IL-12 response by dendritic cells and control of Toxoplasma gondii infection. Cell Reports, v. 43, n. 2, 113795, 2024. doi.org/10.1016/j.celrep.2024.113795. | en_US |
| ISSN | 2211-1247 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/63269 | |
| Language | eng | en_US |
| Publisher | Cell Press | en_US |
| Rights | restricted access | |
| Title | The IRAK1/IRF5 axis initiates IL-12 response by dendritic cells and control of Toxoplasma gondii infection. | en_US |
| Type | Article | |
| Abstract | Activation of endosomal Toll-like receptor (TLR) 7, TLR9, and TLR11/12 is a key event in the resistance against the parasite Toxoplasma gondii. Endosomal TLR engagement leads to expression of interleukin (IL)-12 via the myddosome, a protein complex containing MyD88 and IL-1 receptor-associated kinase (IRAK) 4 in addition to IRAK1 or IRAK2. In murine macrophages, IRAK2 is essential for IL-12 production via endosomal TLRs but, surprisingly, Irak2-/- mice are only slightly susceptible to T. gondii infection, similar to Irak1-/- mice. Here, we report that upon T. gondii infection IL-12 production by different cell populations requires either IRAK1 or IRAK2, with conventional dendritic cells (DCs) requiring IRAK1 and monocyte-derived DCs (MO-DCs) requiring IRAK2. In both populations, we identify interferon regulatory factor 5 as the main transcription factor driving the myddosome-dependent IL-12 production during T. gondii infection. Consistent with a redundant role of DCs and MO-DCs, mutations that affect IL-12 production in both cell populations show high susceptibility to infection in vivo. | en_US |
| Affilliation | Division of Infectious Diseases and Immunology. Department of Medicine. University of Massachusetts Chan Medical School. Worcester, MA, USA. | en_US |
| Affilliation | Department of Molecular, Cell, and Cancer Biology. University of Massachusetts Chan Medical School. Worcester, MA, USA. | en_US |
| Affilliation | Division of Infectious Diseases and Immunology. Department of Medicine. University of Massachusetts Chan Medical School. Worcester, MA, USA. | en_US |
| Affilliation | Division of Infectious Diseases and Immunology. Department of Medicine. University of Massachusetts Chan Medical School. Worcester, MA, USA. | en_US |
| Affilliation | Division of Infectious Diseases and Immunology. Department of Medicine. University of Massachusetts Chan Medical School. Worcester, MA, USA. | en_US |
| Affilliation | Division of Infectious Diseases and Immunology. Department of Medicine. University of Massachusetts Chan Medical School. Worcester, MA, USA. | en_US |
| Affilliation | Division of Infectious Diseases and Immunology. Department of Medicine. University of Massachusetts Chan Medical School. Worcester, MA, USA. | en_US |
| Affilliation | Division of Infectious Diseases and Immunology. Department of Medicine. University of Massachusetts Chan Medical School. Worcester, MA, USA. | en_US |
| Affilliation | Division of Infectious Diseases and Immunology. Department of Medicine. University of Massachusetts Chan Medical School. Worcester, MA, USA/Universidade Federal de Minas Gerais. Centro de Tecnologia de Vacinas. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil. | en_US |
| Subject | CP: Immunology | en_US |
| Subject | CP: Microbiology | en_US |
| Subject | IL-12 | en_US |
| Subject | IRAK | en_US |
| Subject | IRF5 | en_US |
| Subject | Toll-like receptors | en_US |
| Subject | Toxoplasma gondii | en_US |
| Subject | cell signaling | en_US |
| Subject | dendritic cells | en_US |
| Subject | innate immunity | en_US |
| Subject | monocytes | en_US |
| Subject | myddosome | en_US |
| Embargo date | 2025-12-31 | |
