A plasmid-encoded peptide from Staphylococcus aureus induces anti-myeloperoxidase nephritogenic autoimmunity

被引：47

作者：

Ooi, Joshua D. ^{[1
]}

Jiang, Jhih-Hang ^{[2
,3
]}

Eggenhuizen, Peter J. ^{[1
]}

Chua, Ling L. ^{[1
,18
]}

van Timmeren, Mirjan ^{[4
]}

Loh, Khai L. ^{[5
,6
]}

O'Sullivan, Kim M. ^{[1
]}

Gan, Poh Y. ^{[1
]}

Zhong, Yong ^{[1
]}

Tsyganov, Kirill ^{[7
]}

Shochet, Lani R. ^{[1
,8
]}

Ryan, Jessica ^{[1
,8
]}

Stegeman, Coen A. ^{[9
]}

Fugger, Lars ^{[10
,11
]}

Reid, Hugh H. ^{[5
,6
,12
]}

Rossjohn, Jamie ^{[5
,6
,12
,13
]}

Heeringa, Peter ^{[4
]}

Holdsworth, Stephen R. ^{[1
,8
]}

Peleg, Anton Y. ^{[2
,3
,14
,15
]}

Kitching, A. Richard ^{[1
,8
,16
,17
]}

机构：

[1] Monash Univ, Monash Med Ctr, Dept Med, Ctr Inflammatory Dis, Clayton, Vic 3168, Australia

[2] Monash Univ, Monash Biomed Discovery Inst, Infect & Immun Program, Clayton, Vic 3800, Australia

[3] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia

[4] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9700 RB Groningen, Netherlands

[5] Monash Univ, Biomed Discovery Inst, Infect & Immun Program, Clayton, Vic 3800, Australia

[6] Monash Univ, Biomed Discovery Inst, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

[7] Monash Univ, Monash Bioinformat Platform, Clayton, Vic 3800, Australia

[8] Dept Nephrol, Monash Hlth, Clayton, Vic 3168, Australia

[9] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, NL-9700 RB Groningen, Netherlands

[10] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford Ctr Neuroinflammat,Nuffield Dept Clin Neur, Oxford OX3 9DS, England

[11] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford OX3 9DS, England

[12] Monash Univ, Australian Res Council Ctr Excellence Adv Mol Ima, Clayton, Vic 3800, Australia

[13] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales

[14] Monash Univ, Alfred Hosp, Dept Infect Dis, Melbourne, Vic 3004, Australia

[15] Monash Univ, Cent Clin Sch, Melbourne, Vic 3004, Australia

[16] Monash Univ, NHMRC Ctr Personalised Immunol, Clayton, Vic 3168, Australia

[17] Monash Hlth, Dept Pediat Nephrol, Clayton, Vic 3168, Australia

[18] Univ Malaya, Fac Med, Dept Paediat, Kuala Lumpur 50603, Malaysia

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

英国医学研究理事会; 英国惠康基金; 澳大利亚研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

CROSS-REACTIVITY; WEGENERS-GRANULOMATOSIS; RECEPTOR RECOGNITION; INTESTINAL CARRIAGE; NASAL CARRIAGE; IN-VIVO; GLOMERULONEPHRITIS; MYELOPEROXIDASE; AUTOANTIBODIES; ANTIGEN;

D O I：

10.1038/s41467-019-11255-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a Staphylococcus aureus peptide, homologous to an immunodominant MPO T-cell epitope (MPO409-428), can induce anti-MPO autoimmunity. The peptide (6PGD(391-410)) is part of a plasmid-encoded 6-phosphogluconate dehydrogenase found in some S. aureus strains. It induces anti-MPO T-cell autoimmunity and MPO-ANCA in mice, whereas related sequences do not. Mice immunized with 6PGD(391-410), or with S. aureus containing a plasmid expressing 6PGD(391-410), develop glomerulonephritis when MPO is deposited in glomeruli. The peptide induces anti-MPO autoreactivity in the context of three MHC class II allomorphs. Furthermore, we show that 6PGD(391-410) is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD(391-410) antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.

引用

页数：14

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