TREM-2 promotes Th1 responses by interacting with the CD3ζ-ZAP70 complex following Mycobacterium tuberculosis infection

Wu，Yongjian1,2,3,4; Wu，Minhao1; Ming，Siqi1,2,5; Zhan，Xiaoxia1; Hu，Shengfeng1; Li，Xingyu1,2; Yin，Huan1,2; Cao，Can1,2; Liu，Jiao1,2; Li，Jinai1,2; Wu，Zhilong6; Zhou，Jie6; Liu，Lei5; Gong，Sitang4; He，Duanman7; Huang，Xi1,2,3,4,5

2021-09-01

10.1172/JCI137407

JOURNAL OF CLINICAL INVESTIGATION   影响因子和分区

0021-9738

1558-8238

Triggering receptor expressed on myeloid cells 2 (TREM-2) is a modulator of pattern recognition receptors on innate immune cells that regulates the inflammatory response. However, the role of TREM-2 in in vivo models of infection and inflammation remains controversial. Here, we demonstrated that TREM-2 expression on CD4+ T cells was induced by Mycobacterium tuberculosis infection in both humans and mice and positively associated with T cell activation and an effector memory phenotype. Activation of TREM-2 in CD4+ T cells was dependent on interaction with the putative TREM-2 ligand expressed on DCs. Unlike the observation in myeloid cells that TREM-2 signals through DAP12, in CD4+ T cells, TREM-2 interacted with the CD3ζ-ZAP70 complex as well as with the IFN-γ receptor, leading to STAT1/-4 activation and T-bet transcription. In addition, an infection model using reconstituted Rag2 mice (with TREM-2–KO vs. WT cells or TREM-2 vs. TREM-2–CD4+ T cells) or CD4+ T cell–specific TREM-2 conditional KO mice demonstrated that TREM-2 promoted a Th1-mediated host defense against M. tuberculosis infection. Taken together, these findings reveal a critical role of TREM-2 in evoking proinflammatory Th1 responses that may provide potential therapeutic targets for infectious and inflammatory diseases.

SCI

英语

通讯

National Natural Science Foundation of China[82072062,31470877,31670880,81801571] ; National Science and Technology Key Projects for Major Infectious Diseases[2017ZX10302301-002] ; Guangzhou Science and Technology Planning Project[201704020226,201604020006] ; Guangdong Natural Science Foundation[2015A030311009] ; National Key Research and Development Program of China[2016YFC1200105] ; Guangdong Natural Science Fund for Distinguished Young Scholars[2016A030306004] ; Guangzhou Pearl River New Star Program[201610010064] ; Development Project of Foshan Fourth People's Hospital["FSSYKF-2020003","FSSYKF-2020017"] ; Support Scheme of Guangzhou for Leading Talents in Innovation and Entrepreneurship[2017004]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:000755619500001

AMER SOC CLINICAL INVESTIGATION INC

CLINICAL MEDICINE

2-s2.0-85114180400

Scopus

1.Center for Infection and Immunity,Fifth Affiliated Hospital of Sun Yat-sen University,Zhuhai,Guangdong Province,519000,China
2.Guangdong Provincial Engineering Research Center of Molecular Imaging,Guangdong Provincial Key Laboratory of Biomedical Imaging,Department of Interventional Medicine,Fifth Affiliated Hospital,Sun Yat-sen University,Zhuhai,China
3.Southern Marine Science and Engineering Guangdong Laboratory,Zhuhai,Guangdong Province,China
4.Department of Gastroenterology,Guangzhou Women and Children’s Medical Center,Guangzhou Institute of Pediatrics,Guangzhou Medical University,Guangzhou,Guangdong Province,China
5.National Clinical Research Center for Infectious Disease,Shenzhen Third People’s Hospital,Second Affiliated Hospital of the Southern University of Science and Technology,Shenzhen,Guangdong Province,China
6.Fourth People’s Hospital of Foshan,Foshan,China
7.Shantou No. 3 People’s Hospital,Shantou,Guangdong Province,China

Wu，Yongjian,Wu，Minhao,Ming，Siqi,et al. TREM-2 promotes Th1 responses by interacting with the CD3ζ-ZAP70 complex following Mycobacterium tuberculosis infection[J]. JOURNAL OF CLINICAL INVESTIGATION,2021,131(17).

Wu，Yongjian.,Wu，Minhao.,Ming，Siqi.,Zhan，Xiaoxia.,Hu，Shengfeng.,...&Huang，Xi.(2021).TREM-2 promotes Th1 responses by interacting with the CD3ζ-ZAP70 complex following Mycobacterium tuberculosis infection.JOURNAL OF CLINICAL INVESTIGATION,131(17).

Wu，Yongjian,et al."TREM-2 promotes Th1 responses by interacting with the CD3ζ-ZAP70 complex following Mycobacterium tuberculosis infection".JOURNAL OF CLINICAL INVESTIGATION 131.17(2021).