Early introduction of IL-10 weakens BCG revaccination's protection by suppressing CD4+Th1 cell responses

被引：1

作者：

Lei, Qing ^{[1
,2
]}

Fu, Hui ^{[1
,2
]}

Yao, Zongjie ^{[1
,2
]}

Zhou, Zijie ^{[1
,2
,3
]}

Wang, Yueqing ^{[4
]}

Lin, Xiaosong ^{[1
,2
]}

Yuan, Yin ^{[5
]}

Qi, Ouyang ^{[1
,2
]}

Xu, Xinyue ^{[1
,2
]}

Cao, Jinge ^{[1
,2
]}

Gan, Mengze ^{[1
,2
]}

Fan, Xionglin ^{[1
,2
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Pathogen Biol, Wuhan, Peoples R China

[2] Huazhong Univ Sci & Technol, State Key Lab Diag & Treatment Severe Zoonot Infec, Hubei Key Lab Drug Target Res & Pharmacodynam Eval, Wuhan, Peoples R China

[3] Leiden Univ, Med Ctr, Dept Infect Dis, NL-2333 ZA Leiden, Netherlands

[4] Huazhong Univ Sci & Technol, Wuhan 1 Hosp, Tongji Med Coll, Dept Lab Med, Wuhan, Peoples R China

[5] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Pediat, Wuhan, Peoples R China

来源：

JOURNAL OF TRANSLATIONAL MEDICINE | 2024年 / 22卷 / 01期

基金：

中国国家自然科学基金;

关键词：

BCG revaccination; BCG prime-boost strategy; Adult tuberculosis; Primary Mycobacterium tuberculosis infection; IL-10; inhibition; Memory CD4(+) T cell; MYCOBACTERIUM-TUBERCULOSIS INFECTION; VACCINATION; TH1; MICE; MORTALITY; IMMUNITY;

D O I：

10.1186/s12967-024-05683-w

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background The Bacillus Calmette-Gu & eacute;rin (BCG) vaccine, currently the sole authorized vaccine against tuberculosis (TB), demonstrates limited effectiveness in safeguarding adolescents and adults from active TB, even when administered as a booster with either BCG itself or heterologous vaccine candidates. To effectively control the persistent epidemic of adult TB, it is imperative to investigate the mechanisms responsible for the suboptimal efficacy of the BCG prime-boosting strategy against primary Mycobacterium tuberculosis (M.tb) infection. Methods C57BL/6J mice were immunized with the BCG vaccine either once or twice, followed by analysis of lung tissue to assess changes in cytokine levels. Additionally, varying intervals between vaccinations and detection times were examined to study IL-10 expression across different organs. IL-10-expressing cells in the lungs, spleen, and lymph nodes were analyzed through FACS and intracellular cytokine staining (ICS). BCG-revaccinated IL-10-/- mutant mice were compared with wild-type mice to evaluate antigen-specific IgG antibody and T cell responses. Protection against M.tb aerosol challenge was evaluated in BCG-revaccinated mice, either untreated or treated with anti-IL-10R monoclonal antibody. Results IL-10 was significantly upregulated in the lungs of BCG-revaccinated mice shortly after the booster immunization. IL-10 expression peaked in the lungs 3-6 weeks post-revaccination and was also detected in lymph nodes and spleen as early as 2 weeks following the booster dose, regardless of the intervals between the prime and booster vaccinations. The primary sources of IL-10 in these tissues were identified as macrophages and dendritic cells. Blocking IL-10 signaling in BCG-revaccinated mice-either by using IL-10-/- mutant mice or administering anti-IL-10R monoclonal antibody increased levels of antigen-specific IFN-gamma+ or IL-2+ CD4+ T cells, enhanced central and effector memory CD4+ T cell responses, and provided better protection against aerosol infection with 300 CFUs of M.tb. Conclusion Our findings are crucial for formulating effective immunization strategies related to the BCG vaccine and for developing efficacious adult TB vaccines.

引用

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