Sustained IFN-I stimulation impairs MAIT cell responses to bacteria by inducing IL-10 during chronic HIV-1 infection

被引：36

作者：

Tang, X. ^{[1
,2
]}

Zhang, S. ^{[3
,4
]}

Peng, Q. ^{[5
]}

Ling, L. ^{[6
,7
]}

Shi, H. ^{[1
]}

Liu, Y. ^{[1
]}

Cheng, L. ^{[1
,8
]}

Xu, L. ^{[5
]}

Chakrabarti, L. A. ^{[9
]}

Chen, Z. ^{[1
,6
,7
]}

Wang, H. ^{[5
]}

Zhang, Z. ^{[1
,2
,10
,11
,12
]}

机构：

[1] Shenzhen Third Peoples Hosp, Natl Clin Res Ctr Infect Dis, Inst Hepatol, Shenzhen 518112, Guangdong, Peoples R China

[2] South Univ Sci & Technol, Affiliated Hosp 2, Sch Med, Shenzhen 518100, Peoples R China

[3] Fudan Univ, Shanghai Publ Hlth Clin Ctr, Shanghai 201508, Peoples R China

[4] Fudan Univ, Inst Biomed Sci, Shanghai 201508, Peoples R China

[5] Shenzhen Third Peoples Hosp, Dept Infect Dis, Shenzhen 518112, Peoples R China

[6] Univ Hong Kong, Li Ka Shing Fac Med, AIDS Inst, State Key Lab Emerging Infect Dis, Hong Kong, Peoples R China

[7] Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, State Key Lab Emerging Infect Dis, Hong Kong, Peoples R China

[8] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[9] Inst Pasteur, Grp Controle Infect Virales Chron, Unite Virus & Immunite, F-75724 Paris 15, France

[10] Shenzhen Third Peoples Hosp, Guangdong Key Lab Emerging Infect Dis, Shenzhen 518112, Peoples R China

[11] Guangzhou Med Univ, Affiliated Hosp 2, Sch Basic Med Sci, Sino French Hoffmann Inst,Key Lab Immunol, Guangzhou 511436, Peoples R China

[12] Guangzhou Med Univ, Affiliated Hosp 2, Guangdong Prov Key Lab Allergy & Clin Immunol, Guangzhou 511436, Peoples R China

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 08期

基金：

中国国家自然科学基金;

关键词：

INVARIANT T-CELLS; PLASMACYTOID DENDRITIC CELLS; INTERFERON-GAMMA-PRODUCTION; SIV INFECTION; EXPRESSION; INTERLEUKIN-10; ACTIVATION; SUBSET;

D O I：

10.1126/sciadv.aaz0374

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Mucosal-associated invariant T (MAIT) cells in HIV-1-infected individuals are functionally impaired by poorly understood mechanisms. Single-cell transcriptional and surface protein analyses revealed that peripheral MAIT cells from HIV-1-infected subjects were highly activated with the up-regulation of interferon (IFN)-stimulated genes as compared to healthy individuals. Sustained IFN-alpha treatment suppressed MAIT cell responses to Escherichia coli by triggering high-level interleukin-10 (IL-10) production by monocytes, which subsequently inhibited the secretion of IL-12, a crucial costimulatory cytokine for MAIT cell activation. Blocking IFN-alpha or IL-10 receptors prevented MAIT cell dysfunction induced by HIV-1 exposure in vitro. Moreover, blocking the IL-10 receptor significantly improved anti-Mycobacterium tuberculosis responses of MAIT cells from HIV-1-infected patients. Our findings demonstrate the central role of the IFN-I/IL-10 axis in MAIT cell dysfunction during HIV-1 infection, which has implications for the development of anti-IFN-I/IL-10 strategies against bacterial coinfections in HIV-1-infected patients.

引用

页数：12

共 46 条

[1]

Interferon-alpha stimulates production of interleukin-10 in activated CD4(+) T cells and monocytes [J].