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中性粒细胞在抗结核疫苗接种过程中诱导特异性Th1和Th17细胞中的作用

The Role of Neutrophils in the Induction of Specific Th1 and Th17 during Vaccination against Tuberculosis.

作者信息

Trentini Monalisa M, de Oliveira Fábio M, Kipnis André, Junqueira-Kipnis Ana P

机构信息

Laboratory of Immunopathology of Infectious Disease, Department of Microbiology, Immunology, Parasitology and Pathology, Institute of Tropical Disease and Public Health, Federal University of Goiás Goiânia, Brazil.

出版信息

Front Microbiol. 2016 Jun 10;7:898. doi: 10.3389/fmicb.2016.00898. eCollection 2016.

Abstract

Mycobacterium tuberculosis causes tuberculosis (TB), a disease that killed more than 1.5 million people worldwide in 2014, and the Bacillus Calmette Guérin (BCG) vaccine is the only currently available vaccine against TB. However, it does not protect adults. Th1 and Th17 cells are crucial for TB control, as well as the neutrophils that are directly involved in DC trafficking to the draining lymph nodes and the activation of T lymphocytes during infection. Although several studies have shown the importance of neutrophils during M. tuberculosis infection, none have shown its role in the development of a specific response to a vaccine. The vaccine mc(2)-CMX was shown to protect mice against M. tuberculosis challenge, mainly due to specific Th1 and Th17 cells. This study evaluated the importance of neutrophils in the generation of the Th1- and Th17-specific responses elicited by this vaccine. The vaccine injection induced a neutrophil rich lesion with a necrotic central area. The IL-17 KO mice did not generate vaccine-specific Th1 cells. The vaccinated IL-22 KO mice exhibited Th1- and Th17-specific responses. Neutrophil depletion during vaccination abrogated the induction of Th1-specific responses and prohibited the bacterial load reduction observed in the vaccinated animals. The results show, for the first time, the role of neutrophils in the generation of specific Th1 and Th17 cells in response to a tuberculosis vaccine.

摘要

结核分枝杆菌可引发结核病(TB),2014年该疾病在全球导致超过150万人死亡,而卡介苗(BCG)是目前唯一可用的抗结核疫苗。然而,它对成年人并无保护作用。Th1细胞和Th17细胞对于结核病的控制至关重要,在感染期间直接参与树突状细胞(DC)向引流淋巴结的转运以及T淋巴细胞激活的中性粒细胞也同样重要。尽管多项研究已表明中性粒细胞在结核分枝杆菌感染过程中的重要性,但尚无研究表明其在疫苗特异性反应形成中的作用。疫苗mc(2)-CMX被证明可保护小鼠免受结核分枝杆菌攻击,这主要归因于特异性的Th1细胞和Th17细胞。本研究评估了中性粒细胞在该疫苗引发的Th1和Th17特异性反应产生过程中的重要性。疫苗注射引发了一个富含中性粒细胞且中央区域坏死的病灶。白细胞介素-17基因敲除(IL-17 KO)小鼠未产生疫苗特异性Th1细胞。接种疫苗的白细胞介素-22基因敲除(IL-22 KO)小鼠表现出Th1和Th17特异性反应。接种疫苗期间去除中性粒细胞消除了Th1特异性反应的诱导,并阻止了接种疫苗动物体内观察到的细菌载量降低。研究结果首次表明了中性粒细胞在针对结核疫苗产生特异性Th1和Th17细胞过程中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f3d/4901074/1bcf69f77d4c/fmicb-07-00898-g001.jpg

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