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Salmonella exploits HLA-B27 and host unfolded protein responses to promote intracellular replication
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dc.contributor.author | Antoniou, Antony N. | |
dc.contributor.author | Lenart, Izabela | |
dc.contributor.author | Kriston-Vizi, Janos | |
dc.contributor.author | Iwawaki, Takao | |
dc.contributor.author | Turmaine, Mark | |
dc.contributor.author | McHugh, Kirsty | |
dc.contributor.author | Ali, Sadfer | |
dc.contributor.author | Blake, Neil | |
dc.contributor.author | Bowness, Paul | |
dc.contributor.author | Bajaj-Elliott, Mona | |
dc.contributor.author | Gould, Keith | |
dc.contributor.author | Nesbeth, Darren | |
dc.contributor.author | Powis, Simon John | |
dc.date.accessioned | 2018-10-30T16:30:05Z | |
dc.date.available | 2018-10-30T16:30:05Z | |
dc.date.issued | 2019-01 | |
dc.identifier | 255169754 | |
dc.identifier | f4ff63c7-eb89-4a36-8344-98e8062b8109 | |
dc.identifier | 85055489648 | |
dc.identifier | 000455953500022 | |
dc.identifier.citation | Antoniou , A N , Lenart , I , Kriston-Vizi , J , Iwawaki , T , Turmaine , M , McHugh , K , Ali , S , Blake , N , Bowness , P , Bajaj-Elliott , M , Gould , K , Nesbeth , D & Powis , S J 2019 , ' Salmonella exploits HLA-B27 and host unfolded protein responses to promote intracellular replication ' , Annals of the Rheumatic Diseases , vol. 78 , no. 1 , 213532 , pp. 74–82 . https://doi.org/10.1136/annrheumdis-2018-213532 | en |
dc.identifier.issn | 0003-4967 | |
dc.identifier.other | ORCID: /0000-0003-4218-2984/work/60195301 | |
dc.identifier.uri | https://hdl.handle.net/10023/16355 | |
dc.description | A.N.A was funded by ARUK Fellowships Non-Clinical Career Development Fellowship Ref No: 18440. I.L. was funded by an ARUK PhD studentship Ref No: 17868. A.N.A and S.J.P were also in part funded by ARUK (grant 21261) | en |
dc.description.abstract | Objective Salmonella enterica infections can lead to Reactive Arthritis (ReA), which can exhibit an association with human leucocyte antigen (HLA)-B*27:05, a molecule prone to misfolding and initiation of the unfolded protein response (UPR). This study examined how HLA-B*27:05 expression and the UPR affect the Salmonella life-cycle within epithelial cells. Methods Isogenic epithelial cell lines expressing two copies of either HLA-B*27:05 and a control HLA-B*35:01 heavy chain (HC) were generated to determine the effect on the Salmonella infection life-cycle. A cell line expressing HLA-B*27:05.HC physically linked to the light chain beta-2-microglobulin and a specific peptide (referred to as a single chain trimer, SCT) was also generated to determine the effects of HLA-B27 folding status on S. enterica life-cycle. XBP-1 venus and AMP dependent Transcription Factor (ATF6)-FLAG reporters were used to monitor UPR activation in infected cells. Triacin C was used to inhibit de novo lipid synthesis during UPR, and confocal imaging of ER tracker stained membrane allowed quantification of glibenclamide-associated membrane. Results S. enterica demonstrated enhanced replication with an altered cellular localisation in the presence of HLA-B*27:05.HC but not in the presence of HLA-B*27:05.SCT or HLA-B*35:01. HLA-B*27:05.HC altered the threshold for UPR induction. Salmonella activated the UPR and required XBP-1 for replication, which was associated with endoreticular membrane expansion and lipid metabolism. Conclusions HLA-B27 misfolding and a UPR cellular environment are associated with enhanced Salmonella replication, while Salmonella itself can activate XBP-1 and ATF6. These data provide a potential mechanism linking the life-cycle of Salmonella with the physicochemical properties of HLA-B27 and cellular events that may contribute to ReA pathogenesis. Our observations suggest that the UPR pathway maybe targeted for future therapeutic intervention. | |
dc.format.extent | 9 | |
dc.format.extent | 4148728 | |
dc.language.iso | eng | |
dc.relation.ispartof | Annals of the Rheumatic Diseases | en |
dc.subject | QR Microbiology | en |
dc.subject | RC Internal medicine | en |
dc.subject | NDAS | en |
dc.subject | BDC | en |
dc.subject | R2C | en |
dc.subject.lcc | QR | en |
dc.subject.lcc | RC | en |
dc.title | Salmonella exploits HLA-B27 and host unfolded protein responses to promote intracellular replication | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. Cellular Medicine Division | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Centre for Biophotonics | en |
dc.identifier.doi | 10.1136/annrheumdis-2018-213532 | |
dc.description.status | Peer reviewed | en |
dc.date.embargoedUntil | 2018-10-24 |
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