文献类型：期刊文献

英文题名：Severe persistent mycobacteria antigen stimulation causes lymphopenia through impairing hematopoiesis

作者：Li, Fei[1,2];Ma, Yanlin[1,2];Li, Xiaoping[3];Zhang, Dan[1,2];Han, Jiangyuan[1,2];Tan, Daquan[1,2];Mi, Youjun[1,2,4];Yang, Xiaojuan[1,2,5];Wang, Juan[1,2];Zhu, Bingdong[1,2,6]

第一作者：Li, Fei

通信作者：Zhu, BD[1];Zhu, BD[2];Zhu, BD[3]

机构：[1]Lanzhou Univ, Inst Pathogen Biol, Sch Basic Med Sci, Gansu Prov Key Lab Evidence Based Med & Clin Trans, Lanzhou, Peoples R China;[2]Lanzhou Univ, Inst Pathogen Biol, Lanzhou Ctr TB Res, Sch Basic Med Sci, Lanzhou, Peoples R China;[3]Lanzhou Pulm Hosp, Inpatient Ward 1, Lanzhou, Peoples R China;[4]Lanzhou Univ, Inst Pathophysiol, Sch Basic Med Sci, Lanzhou, Peoples R China;[5]Gansu Univ Tradit Chinese Med, Dept Clin Med, Lanzhou, Peoples R China;[6]Lanzhou Univ, Coll Vet Med, State Key Lab Vet Etiol Biol, Lanzhou, Peoples R China

第一机构：Lanzhou Univ, Inst Pathogen Biol, Sch Basic Med Sci, Gansu Prov Key Lab Evidence Based Med & Clin Trans, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Inst Pathogen Biol, Sch Basic Med Sci, Gansu Prov Key Lab Evidence Based Med & Clin Trans, Lanzhou, Peoples R China;[2]corresponding author), Lanzhou Univ, Inst Pathogen Biol, Lanzhou Ctr TB Res, Sch Basic Med Sci, Lanzhou, Peoples R China;[3]corresponding author), Lanzhou Univ, Coll Vet Med, State Key Lab Vet Etiol Biol, Lanzhou, Peoples R China.

年份：2023

卷号：13

外文期刊名：FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY

收录：;Scopus(收录号：2-s2.0-85147220059);WOS:【SCI-EXPANDED(收录号:WOS:000919975100001)】；

基金：Funding This work was funded by National Key Research and Development Program of China (2021YFC2301503), Youth Science Fund Project of the National Natural Science Foundation of China (82001675), the Fundamental Research Funds for the Central Universities of the Lanzhou University (lzujbky-2021-4), and Gansu Science and Technology Project of China (21JR7RA534).

语种：英文

外文关键词：mycobacterium tuberculosis; miliary tuberculosis; BCG; hematopoiesis; lymphopenia; IL-7

摘要：Miliary tubersculosis (TB), an acute systemic blood disseminated tuberculosis mainly caused by Mycobacterium tuberculosis (M. tuberculosis), can cause signs of lymphopenia in clinical patients. To investigate whether/how persistent mycobacteria antigen stimulation impairs hematopoiesis and the therapeutic effect of interleukin-7 (IL-7), a mouse model of Mycobacterium Bovis Bacillus Calmette-Guerin (BCG) intravenous infection with/without an additional stimulation with M. tuberculosis multi-antigen cocktail containing ESAT6-CFP10 (EC) and Mtb10.4-HspX (MH) was established. Consistent with what happened in miliary TB, high dose of BCG intravenous infection with/without additional antigen stimulation caused lymphopenia in peripheral blood. In which, the levels of cytokines IFN-gamma and TNF-alpha in serum increased, and consequently the expression levels of transcription factors Batf2 and IRF8 involved in myeloid differentiation were up-regulated, while the expression levels of transcription factors GATA2 and NOTCH1 involved in lymphoid commitment were down-regulated, and the proliferating activity of bone marrow (BM) lineage(-) c-Kit(+) (LK) cells decreased. Furthermore, recombinant Adeno-Associated Virus 2-mediated IL-7 (rAAV2-IL-7) treatment could significantly promote the elevation of BM lymphoid progenitors. It suggests that persistent mycobacteria antigen stimulation impaired lymphopoiesis of BM hematopoiesis, which could be restored by complement of IL-7.