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The UPR sensor IRE1 alpha promotes dendritic cell responses to control Toxoplasma gondii infection

Anais F. Poncet, Victor Bosteels (UGent) , Eik Hoffmann, Sylia Chehade, Sofie Rennen (UGent) , Ludovic Huot, Veronique Peucelle, Sandra Maréchal (UGent) , Jamal Khalife, Nicolas Blanchard, et al.
(2021) EMBO REPORTS. 22(3).
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Organization
Abstract
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 IRE1 alpha pathway and the inhibition of the ATF6 pathway. Induction of XBP1s controls pro-inflammatory cytokine secretion in infected DCs, while IRE1 alpha promotes MHCI antigen presentation of secreted parasite antigens. In mice, infection leads to a specific activation of the IRE1 alpha pathway, which is restricted to the cDC1 subset. Mice deficient for IRE1 alpha 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 IRE1 alpha/XBP1s branch of the UPR as a key regulator of host defense upon T. gondii infection.
Keywords
antigen presentation, cytokines, dendritic cells, Toxoplasma gondii, UPR

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Citation

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MLA
Poncet, Anais F., et al. “The UPR Sensor IRE1 Alpha Promotes Dendritic Cell Responses to Control Toxoplasma Gondii Infection.” EMBO REPORTS, vol. 22, no. 3, 2021, doi:10.15252/embr.201949617.
APA
Poncet, A. F., Bosteels, V., Hoffmann, E., Chehade, S., Rennen, S., Huot, L., … Marion, S. (2021). The UPR sensor IRE1 alpha promotes dendritic cell responses to control Toxoplasma gondii infection. EMBO REPORTS, 22(3). https://doi.org/10.15252/embr.201949617
Chicago author-date
Poncet, Anais F., Victor Bosteels, Eik Hoffmann, Sylia Chehade, Sofie Rennen, Ludovic Huot, Veronique Peucelle, et al. 2021. “The UPR Sensor IRE1 Alpha Promotes Dendritic Cell Responses to Control Toxoplasma Gondii Infection.” EMBO REPORTS 22 (3). https://doi.org/10.15252/embr.201949617.
Chicago author-date (all authors)
Poncet, Anais F., Victor Bosteels, Eik Hoffmann, Sylia Chehade, Sofie Rennen, Ludovic Huot, Veronique Peucelle, Sandra Maréchal, Jamal Khalife, Nicolas Blanchard, Sophie Janssens, and Sabrina Marion. 2021. “The UPR Sensor IRE1 Alpha Promotes Dendritic Cell Responses to Control Toxoplasma Gondii Infection.” EMBO REPORTS 22 (3). doi:10.15252/embr.201949617.
Vancouver
1.
Poncet AF, Bosteels V, Hoffmann E, Chehade S, Rennen S, Huot L, et al. The UPR sensor IRE1 alpha promotes dendritic cell responses to control Toxoplasma gondii infection. EMBO REPORTS. 2021;22(3).
IEEE
[1]
A. F. Poncet et al., “The UPR sensor IRE1 alpha promotes dendritic cell responses to control Toxoplasma gondii infection,” EMBO REPORTS, vol. 22, no. 3, 2021.
@article{8712046,
  abstract     = {{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 IRE1 alpha pathway and the inhibition of the ATF6 pathway. Induction of XBP1s controls pro-inflammatory cytokine secretion in infected DCs, while IRE1 alpha promotes MHCI antigen presentation of secreted parasite antigens. In mice, infection leads to a specific activation of the IRE1 alpha pathway, which is restricted to the cDC1 subset. Mice deficient for IRE1 alpha 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 IRE1 alpha/XBP1s branch of the UPR as a key regulator of host defense upon T. gondii infection.}},
  articleno    = {{e49617}},
  author       = {{Poncet, Anais F. and Bosteels, Victor and Hoffmann, Eik and Chehade, Sylia and Rennen, Sofie and Huot, Ludovic and Peucelle, Veronique and Maréchal, Sandra and Khalife, Jamal and Blanchard, Nicolas and Janssens, Sophie and Marion, Sabrina}},
  issn         = {{1469-221X}},
  journal      = {{EMBO REPORTS}},
  keywords     = {{antigen presentation,cytokines,dendritic cells,Toxoplasma gondii,UPR}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{17}},
  title        = {{The UPR sensor IRE1 alpha promotes dendritic cell responses to control Toxoplasma gondii infection}},
  url          = {{http://dx.doi.org/10.15252/embr.201949617}},
  volume       = {{22}},
  year         = {{2021}},
}
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