Mucosal exposure to non-tuberculous mycobacteria elicits B cell-mediated immunity against pulmonary tuberculosis.
Mucosal exposure to non-tuberculous mycobacteria elicits B cell-mediated immunity against pulmonary tuberculosis.
复制标题
粘膜暴露于非结核分枝杆菌促成B细胞介导的肺结核的免疫力。
DOI：
10.1016/j.celrep.2022.111783
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发表时间：
2022-12-13
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
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作者：
卡介苗(BCG)是唯一获得许可的针对结核分枝杆菌(Mtb)的疫苗，结核分枝杆菌是结核病的病原体。然而，卡介苗的疗效有限，需要开发更好的疫苗。非结核分枝杆菌(NTM)广泛存在于环境中，可能是机会性的病原体。结核病流行国家的个人暴露于NTM的风险较高，但之前的研究尚未阐明NTM暴露与卡介苗抗结核疗效之间的关系。因此，我们建立了一种小鼠模型(BCG+NTM)来模拟人BCG免疫方案和NTM的持续暴露。与单独使用BCG相比，BCG+NTM小鼠对肺结核病表现出更好和更持久的保护，B细胞内流和血清和呼吸道中的抗Mtb抗体增加。值得注意的是，空间转录和免疫组织化学显示，BCG+NTM小鼠形成具有生发中心发育特征的B细胞聚集体，这与减少结核分枝杆菌负担相关。我们的研究表明，接触NTM和结核病保护之间存在直接关系，其中B细胞起着关键作用。
Bacille Calmette Guerin (BCG) is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) disease. However, BCG has limited efficacy, necessitating development of better vaccines. Non-tuberculous mycobacteria (NTM), ubiquitously present in the environment, can be opportunistic pathogens. Individuals in TB endemic countries experience higher exposure to NTM, but previous studies have not elucidated the relationship between NTM exposure and BCG efficacy against TB. Therefore, we developed a mouse model (BCG+NTM) to simulate human BCG immunization regime and continuous NTM exposure. BCG+NTM mice exhibit superior and prolonged protection against pulmonary TB, with increase in B-cell influx and anti-Mtb antibodies in serum and airways, compared to BCG alone. Notably, spatial transcriptomics and immunohistochemistry reveal that BCG+NTM mice form B-cell aggregates with features of germinal center development, which correlates with reduced Mtb burden. Our studies suggest a direct relationship between NTM exposure and TB protection, with B-cells playing a crucial role.
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影响因子：
7.3
作者：
Dockrell HM;Smith SG
通讯作者：
Smith SG
影响因子：
3.1
作者：
Brandt, L;Cunha, JF;Andersen, P
通讯作者：
Andersen, P
DOI：
10.1016/s2213-2600(22)00092-3
发表时间：
2022-06
期刊：
The Lancet. Respiratory medicine
影响因子：
--
作者：
Dheda K;Perumal T;Moultrie H;Perumal R;Esmail A;Scott AJ;Udwadia Z;Chang KC;Peter J;Pooran A;von Delft A;von Delft D;Martinson N;Loveday M;Charalambous S;Kachingwe E;Jassat W;Cohen C;Tempia S;Fennelly K;Pai M
通讯作者：
Pai M
影响因子：
--
作者：
Ancelet, Lindsay;Kirman, Joanna
通讯作者：
Kirman, Joanna
DOI：
10.1016/j.ijid.2021.02.107
发表时间：
2021-12
期刊：
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
影响因子：
--
作者：
Chakaya J;Khan M;Ntoumi F;Aklillu E;Fatima R;Mwaba P;Kapata N;Mfinanga S;Hasnain SE;Katoto PDMC;Bulabula ANH;Sam-Agudu NA;Nachega JB;Tiberi S;McHugh TD;Abubakar I;Zumla A
通讯作者：
Zumla A