Mucosal Therapy of Multi-Drug Resistant Tuberculosis With IgA and Interferon-γ.
Mucosal Therapy of Multi-Drug Resistant Tuberculosis With IgA and Interferon-γ.
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DOI：
10.3389/fimmu.2020.582833
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发表时间：
2020
影响因子：
7.3
通讯作者：
Reljic R
中科院分区：
文献类型：
--
作者：
Tran AC;Diogo GR;Paul MJ;Copland A;Hart P;Mehta N;Irvine EB;Mussá T;Drake PMW;Ivanyi J;Alter G;Reljic R
新的证据表明，抗体在各种结核病实验模型中具有保护作用。在这里，我们报道了在转人IgA受体CD89的小鼠中，利用针对α -结晶蛋白（Acr, HspX）抗原的人单克隆IgA 2E9抗体和小鼠干扰素γ的组合，对耐多药结核分枝杆菌（MDR-TB）感染的保护作用。黏膜IgA和IFN-γ联合作用的研究当在感染时应用治疗时，治疗效果最强（减少50倍），但即使在感染已经建立后开始治疗时，也观察到肺部细菌负荷的统计学显着减少。由于用IgG版本的2E9抗体对人IgG受体CD64转基因小鼠无效，因此通过增强吞噬和中性粒细胞介导的对感染细胞的杀伤的保护作用是IgA同型介导的。与缺乏针对毒力相关的MPT64抗原的IgA抗体不同，IgA抗体对人类的Acr抗原保护的特异性已通过其在潜伏性结核病中升高的血清水平得到证实。我们的研究结果为黏膜免疫疗法治疗耐多药结核病提供了第一个潜在的证据。
New evidence has been emerging that antibodies can be protective in various experimental models of tuberculosis. Here, we report on protection against multidrug-resistant Mycobacterium tuberculosis (MDR-TB) infection using a combination of the human monoclonal IgA 2E9 antibody against the alpha-crystallin (Acr, HspX) antigen and mouse interferon-gamma in mice transgenic for the human IgA receptor, CD89. The effect of the combined mucosal IgA and IFN-γ; treatment was strongest (50-fold reduction) when therapy was applied at the time of infection, but a statistically significant reduction of lung bacterial load was observed even when the therapy was initiated once the infection had already been established. The protection involving enhanced phagocytosis and then neutrophil mediated killing of infected cells was IgA isotype mediated, because treatment with an IgG version of 2E9 antibody was not effective in human IgG receptor CD64 transgenic mice. The Acr antigen specificity of IgA antibodies for protection in humans has been indicated by their elevated serum levels in latent tuberculosis unlike the lack of IgA antibodies against the virulence-associated MPT64 antigen. Our results represent the first evidence for potential translation of mucosal immunotherapy for the management of MDR-TB.
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DOI：
10.4049/jimmunol.1003189
发表时间：
2011-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Balu S;Reljic R;Lewis MJ;Pleass RJ;McIntosh R;van Kooten C;van Egmond M;Challacombe S;Woof JM;Ivanyi J
通讯作者：
Ivanyi J
影响因子：
6.7
作者：
Prados-Rosales R;Carreño L;Cheng T;Blanc C;Weinrick B;Malek A;Lowary TL;Baena A;Joe M;Bai Y;Kalscheuer R;Batista-Gonzalez A;Saavedra NA;Sampedro L;Tomás J;Anguita J;Hung SC;Tripathi A;Xu J;Glatman-Freedman A;Jacobs WR Jr;Chan J;Porcelli SA;Achkar JM;Casadevall A
通讯作者：
Casadevall A
影响因子：
30.3
作者：
Achkar JM;Casadevall A
通讯作者：
Casadevall A
影响因子：
64.8
作者：
Pethe, K;Alonso, S;Menozzi, FD
通讯作者：
Menozzi, FD
DOI：
10.1073/pnas.1611776114
发表时间：
2017-05-09
影响因子：
11.1
作者：
Li, Hao;Wang, Xing-xing;Javid, Babak
通讯作者：
Javid, Babak