Author:
Xu Zhengzhong,Li Xin,Xia Aihong,Zhang Zhifang,Wan Jiaxu,Gao Yan,Meng Chuang,Chen Xiang,Jiao Xin-an
Abstract
Abstract
Background
Control of Tuberculosis (TB) infection is mainly the result of productive teamwork between T-cell populations and antigen presenting cells (APCs). However, APCs activation at the site of initiating cellular immune response during BCG early infection is not completely understood.
Methods
In this study, we injected C57BL/6 mice in intravenous (i.v) or subcutaneous (s.c) route, then splenic or inguinal lymph node (LN) DCs and MΦs were sorted, and mycobacteria uptake, cytokine production, antigen presentation activity, and cell phenotype were investigated and compared, respectively.
Results
Ag85A-specific T-cell immune response began at 6 days post BCG infection, when BCG was delivered in s.c route, Th17 immune response could be induced in inguinal LN. BCG could induce high level of activation phenotype in inguinal LN MΦs, while the MHC II presentation of mycobacteria-derived peptides by DCs was more efficient than MΦs.
Conclusions
The results showed that BCG immunized route can decide the main tissue of T-cell immune response. Compared with s.c injected route, APCs undergo more rapid cell activation in spleen post BCG i.v infection.
Funder
the National Key Research and Development Program of China
the Natural Science Foundation of Jiangsu Province
the Jiangsu Agriculture Science and Technology Innovation Fund
Publisher
Springer Science and Business Media LLC
Reference34 articles.
1. WHO. : Global Tuberculosis Report 2021. Available from: https://wwww.hoint/publications/en/ 2021.
2. Singh AK, Praharaj M, Lombardo KA, Yoshida T, Matoso A, Baras AS, Zhao L, Srikrishna G, Huang J, Prasad P, et al. Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against Bladder cancer. Nat Commun. 2022;13(1):878.
3. Darrah PA, Zeppa JJ, Maiello P, Hackney JA, Wadsworth MH 2nd, Hughes TK, Pokkali S, Swanson PA 2nd, Grant NL, Rodgers MA, et al. Prevention of Tuberculosis in macaques after intravenous BCG immunization. Nature. 2020;577(7788):95–102.
4. Barclay WR, Anacker RL, Brehmer W, Leif W, Ribi E. Aerosol-Induced Tuberculosis in Subhuman Primates and the course of the Disease after Intravenous BCG Vaccination. Infect Immun. 1970;2(5):574–82.
5. Anacker RL, Brehmer W, Barclay WR, Leif WR, Ribi E, Simmons JH, Smith AW. Superiority of intravenously administered BCG and BCG cell walls in protecting rhesus monkeys (Macaca mulatta) against airborne Tuberculosis. Z Immunitatsforsch Exp Klin Immunol. 1972;143(4):363–76.