| First Author | Poncet AF | Year | 2021 |
| Journal | EMBO Rep | Volume | 22 |
| Issue | 3 | Pages | e49617 |
| PubMed ID | 33586853 | Mgi Jnum | J:321018 |
| Mgi Id | MGI:6712135 | Doi | 10.15252/embr.201949617 |
| Citation | Poncet AF, et al. (2021) The UPR sensor IRE1alpha promotes dendritic cell responses to control Toxoplasma gondii infection. EMBO Rep 22(3):e49617 |
| abstractText | The unfolded protein response (UPR) has emerged as a central regulator of immune cell responses in several pathologic contexts including infections. However, how intracellular residing pathogens modulate the UPR in dendritic cells (DCs) and thereby affect T cell-mediated immunity remains uncharacterized. Here, we demonstrate that infection of DCs with Toxoplasma gondii (T. gondii) triggers a unique UPR signature hallmarked by the MyD88-dependent activation of the IRE1alpha pathway and the inhibition of the ATF6 pathway. Induction of XBP1s controls pro-inflammatory cytokine secretion in infected DCs, while IRE1alpha promotes MHCI antigen presentation of secreted parasite antigens. In mice, infection leads to a specific activation of the IRE1alpha pathway, which is restricted to the cDC1 subset. Mice deficient for IRE1alpha and XBP1 in DCs display a severe susceptibility to T. gondii and succumb during the acute phase of the infection. This early mortality is correlated with increased parasite burden and a defect in splenic T-cell responses. Thus, we identify the IRE1alpha/XBP1s branch of the UPR as a key regulator of host defense upon T. gondii infection. |
