Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection

被引：9

作者：

Cooper, Lucy ^{[1
,2
]}

Xu, Hui ^{[1
,2
]}

Polmear, Jack ^{[1
,2
]}

Kealy, Liam ^{[1
,2
]}

Szeto, Christopher ^{[2
,3
]}

Pang, Ee Shan ^{[1
,2
]}

Gupta, Mansi ^{[4
]}

Kirn, Alana ^{[1
,2
]}

Taylor, Justin J. ^{[5
]}

Jackson, Katherine J. L. ^{[6
]}

Broomfield, Benjamin J. ^{[7
,8
]}

Nguyen, Angela ^{[1
,2
]}

Grac, Catarina Gago da ^{[7
]}

La Gruta, Nicole ^{[1
,2
]}

Utzschneider, Daniel T. ^{[7
]}

Groom, Joanna R. ^{[8
,9
]}

Martelotto, Luciano ^{[10
,11
]}

Parish, Ian A. ^{[12
,13
,14
,15
]}

O'Keeffe, Meredith ^{[1
,2
]}

Scharer, Christopher D. ^{[3
]}

Gras, Stephanie ^{[3
]}

Good-Jacobson, Kim L. ^{[1
,2
]}

机构：

[1] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia

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

[3] La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem & Chem, Melbourne, Vic, Australia

[4] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA USA

[5] Fred Hutchinson Canc Ctr, Vaccine & Infect Dis Div, Seattle, WA USA

[6] Garvan Inst Med Res, Darlinghurst, NSW, Australia

[7] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia

[8] Walter & Eliza Hall Inst Med Res, Div Immunol, Parkville, Vic, Australia

[9] Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia

[10] Univ Adelaide, Fac Hlth & Med Sci, Adelaide Ctr Epigenet, Adelaide, SA, Australia

[11] Univ Adelaide, South Australian Immunogen Canc Inst, Fac Hlth & Med Sci, Adelaide, SA, Australia

[12] Univ Melbourne, Victorian Comprehens Canc Ctr, Ctr Canc Res, Melbourne, Vic, Australia

[13] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[14] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic, Australia

[15] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT, Australia

来源：

IMMUNITY | 2024年 / 57卷 / 05期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

FACTOR T-BET; GERMINAL-CENTER; BOOSTER VACCINATION; RESPONSES; EXHAUSTION; EXPRESSION; DIFFERENTIATION; DISEASE; VIRUS; TRANSCRIPTOME;

D O I：

10.1016/j.immuni.2024.03.016

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Memory B cells (MBCs) are key providers of long-lived immunity against infectious disease, yet in chronic viral infection, they do not produce effective protection. How chronic viral infection disrupts MBC development and whether such changes are reversible remain unknown. Through single -cell (sc)ATAC-seq and scRNA-seq during acute versus chronic lymphocytic choriomeningitis viral infection, we identified a memory subset enriched for interferon (IFN)-stimulated genes (ISGs) during chronic infection that was distinct from the T -bet + subset normally associated with chronic infection. Blockade of IFNAR-1 early in infection transformed the chromatin landscape of chronic MBCs, decreasing accessibility at ISG-inducing transcription factor binding motifs and inducing phenotypic changes in the dominating MBC subset, with a decrease in the ISG subset and an increase in CD11c + CD80 + cells. However, timing was critical, with MBCs resistant to intervention at 4 weeks post -infection. Together, our research identifies a key mechanism to instruct MBC identity during viral infection.

引用

页码：1037 / 1055.e6

页数：26

共 122 条

[1] Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation [J].