Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient Mice.
Immune Correlates of Disseminated BCG Infection in IL12RB1-Deficient Mice.
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DOI：
10.3390/vaccines10071147
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发表时间：
2022-07-19
期刊：
影响因子：
7.8
通讯作者：
Wan, Yanmin
中科院分区：
文献类型：
--
作者：
Wang, Xuyang;Jia, Liqiu;Liu, Yang;Wang, Jing;Qiu, Chao;Li, Tao;Zhang, Wenhong;Zhu, Zhaoqin;Wu, Jing;Wan, Yanmin
白介素 12 受体 β1 (IL12RB1) 缺陷个体对局部或播散性 BCG 感染和环境分枝杆菌感染的易感性增加。然而，IL12RB1缺乏症的低临床外显率和分枝杆菌感染的低复发率表明该人群中仍然存在保护性免疫。在本研究中，我们使用 IL12RB1 缺陷小鼠模型研究了结核病抑制机制。我们的结果表明，Il12rb1−/− 小鼠的脾脏和肺中的 CFU 计数显着增加，特别是当皮下接种 BCG（丹麦株）时。 Il12rb1−/− 小鼠肺部先天性 TNF-a 和 IFN-γ 反应下降，而 IL-17 反应显着增加。我们还发现 Il12rb1−/− 小鼠中 PPD 特异性 IFN-γ 释放受到损害，但特异性 TNF-a 释放并未受到损害，并且抗体反应显着增强。此外，相关性分析显示，先天性和 PPD 特异性 IFN-γ 反应均与 CFU 计数呈正相关，而先天性 IL-12a 水平与 Il12rb1−/− 小鼠肺部的 CFU 计数呈负相关。总的来说，这些发现证明，Il12rb1−/− 小鼠中针对分枝杆菌的适应性免疫并未完全消失。此外，我们的结果表明，在 IL12RB1 缺乏的情况下，单独使用 IFN-γ 反应可能无法抑制 BCG 炎。
Interleukin-12 receptor β1 (IL12RB1)-deficient individuals show increased susceptibilities to local or disseminated BCG infection and environmental mycobacteria infection. However, the low clinical penetrance of IL12RB1 deficiency and low recurrence rate of mycobacteria infection suggest that protective immunity still exists in this population. In this study, we investigated the mechanism of tuberculosis suppression using the IL12RB1-deficient mouse model. Our results manifested that Il12rb1−/− mice had significantly increased CFU counts in spleens and lungs, especially when BCG (Danish strain) was inoculated subcutaneously. The innate TNF-a and IFN-γ responses decreased, while the IL-17 responses increased significantly in the lungs of Il12rb1−/− mice. We also found that PPD-specific IFN-γ release was impaired in Il12rb1−/− mice, but the specific TNF-a release was not compromised, and the antibody responses were significantly enhanced. Moreover, correlation analyses revealed that both the innate and PPD-specific IFN-γ responses positively correlated with CFU counts, whereas the innate IL-12a levels negatively correlated with CFU counts in Il12rb1−/− mice lungs. Collectively, these findings proved that the adaptive immunities against mycobacteria are not completely nullified in Il12rb1−/− mice. Additionally, our results imply that IFN-γ responses alone might not be able to contain BCGitis in the setting of IL12RB1 deficiency.
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DOI：
10.1084/jem.20021769
发表时间：
2003-02-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fieschi C;Dupuis S;Catherinot E;Feinberg J;Bustamante J;Breiman A;Altare F;Baretto R;Le Deist F;Kayal S;Koch H;Richter D;Brezina M;Aksu G;Wood P;Al-Jumaah S;Raspall M;Da Silva Duarte AJ;Tuerlinckx D;Virelizier JL;Fischer A;Enright A;Bernhöft J;Cleary AM;Vermylen C;Rodriguez-Gallego C;Davies G;Blütters-Sawatzki R;Siegrist CA;Ehlayel MS;Novelli V;Haas WH;Levy J;Freihorst J;Al-Hajjar S;Nadal D;De Moraes Vasconcelos D;Jeppsson O;Kutukculer N;Frecerova K;Caragol I;Lammas D;Kumararatne DS;Abel L;Casanova JL
通讯作者：
Casanova JL
影响因子：
3.7
作者：
Katayama M;Ohmura K;Yukawa N;Terao C;Hashimoto M;Yoshifuji H;Kawabata D;Fujii T;Iwakura Y;Mimori T
通讯作者：
Mimori T
DOI：
10.4049/jimmunol.1100123
发表时间：
2011-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lin AM;Rubin CJ;Khandpur R;Wang JY;Riblett M;Yalavarthi S;Villanueva EC;Shah P;Kaplan MJ;Bruce AT
通讯作者：
Bruce AT
影响因子：
--
作者：
Dhiman, N.;Ovsyannikova, G.;Poland, G. A.
通讯作者：
Poland, G. A.
影响因子：
4.4
作者：
Kouadjo KE;Nishida Y;Cadrin-Girard JF;Yoshioka M;St-Amand J
通讯作者：
St-Amand J