| First Author | Pereira M | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 2 | Pages | 113795 |
| PubMed ID | 38367238 | Mgi Jnum | J:347749 |
| Mgi Id | MGI:7613944 | Doi | 10.1016/j.celrep.2024.113795 |
| Citation | Pereira M, et al. (2024) The IRAK1/IRF5 axis initiates IL-12 response by dendritic cells and control of Toxoplasma gondii infection. Cell Rep 43(2):113795 |
| abstractText | 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. |
