Journal article
NOD2 and TLR2 signal via TBK1 and PI31 to direct cross-presentation and CD8 T cell responses
- Abstract:
- NOD2 and TLR2 recognize components of bacterial cell wall peptidoglycan and direct defense against enteric pathogens. CD8+ T cells are important for immunity to such pathogens but how NOD2 and TLR2 induce antigen specific CD8+ T cell responses is unknown. Here, we define how these pattern recognition receptors (PRRs) signal in primary dendritic cells (DCs) to influence MHC class I antigen presentation. We show NOD2 and TLR2 phosphorylate PI31 via TBK1 following activation in DCs. PI31 interacts with TBK1 and Sec16A at endoplasmic reticulum exit sites (ERES), which positively regulates MHC class I peptide loading and immunoproteasome stability. Following NOD2 and TLR2 stimulation, depletion of PI31 or inhibition of TBK1 activity in vivo impairs DC cross-presentation and CD8+ T cell activation. DCs from Crohn's patients expressing NOD2 polymorphisms show dysregulated cross-presentation and CD8+ T cell responses. Our findings reveal unidentified mechanisms that underlie CD8+ T cell responses to bacteria in health and in Crohn's.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 12.4MB, Terms of use)
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- Publisher copy:
- 10.3389/fimmu.2019.00958
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Immunology More from this journal
- Volume:
- 10
- Publication date:
- 2019-04-30
- Acceptance date:
- 2019-04-15
- DOI:
- ISSN:
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1664-3224
- Keywords:
- Pubs id:
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pubs:998154
- UUID:
-
uuid:d59ae326-835e-4c2e-934c-53970b2af4ea
- Local pid:
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pubs:998154
- Source identifiers:
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998154
- Deposit date:
-
2019-05-16
Terms of use
- Copyright holder:
- Corridoni et al
- Copyright date:
- 2019
- Notes:
- © 2019 Corridoni, Shiraishi, Chapman, Steevels, Muraro, Thézénas, Prota, Chen, Gileadi, Ternette, Cerundolo and Simmons. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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