da Costa Adeliane C, de Resende Danilo P, Santos Bruno de P O, Zoccal Karina F, Faccioli Lúcia H, Kipnis André, Junqueira-Kipnis Ana P
Laboratory of Immunopathology of Infectious Disease, Department of Microbiology, Immunology, Parasitology and Pathology, Tropical Institute of Pathology and Public Health, Federal University of GoiásGoiânia, Brazil.
Laboratory of Inflammation and Immunology of Parasitoses, Department of Clinical, Toxicological and Bromatological Analyses, School of Pharmaceutical Sciences of Ribeirão Preto, University of São PauloSão Paulo, Brazil.
Front Microbiol. 2017 Apr 12;8:623. doi: 10.3389/fmicb.2017.00623. eCollection 2017.
Bacillus Calmette-Guérin (BCG) is a vaccine used to prevent tuberculosis (TB). Due to the poor protection conferred by BCG in adults, new, more effective formulations have been developed. A recombinant BCG vaccine expressing the CMX fusion protein Ag85c_MPT51_HspX (rBCG-CMX) induced Th1 and Th17 responses and provided better protection than BCG. It has been shown that expressing CMX also induces better protection than BCG and is a strong macrophage activator. The aim of the present study was to evaluate macrophage activation by the recombinant CMX fusion protein and by rBCG-CMX and to evaluate their ability to generate vaccine-specific immune responses. The results demonstrate that rCMX protein expressed by BCG (rBCG-CMX) activates pulmonary macrophages; increases the expression of activation molecules, cytokines, and MHC-II. The interaction with rCMX activates the transcription factor NF-κB and induces the production of the cytokines TGF-β, TNF-α, and IL-6. The stimulation of bone marrow-derived macrophages (BMMs) from TLR-4 or TLR-2 KO mice showed that in the absence of TLR-4, IL-6 was not produced. rBCG-CMX was unable to induce CMX-specific Th1 and Th17 cells in TLR-4 and TLR-2 KO mice, suggesting that these receptors participate in their induction. We concluded that both the rBCG-CMX vaccine and the rCMX protein can activate macrophages and favor the specific immune response necessary for this vaccine.
卡介苗（BCG）是一种用于预防结核病（TB）的疫苗。由于卡介苗在成人中提供的保护效果不佳，因此已开发出新型、更有效的制剂。一种表达CMX融合蛋白Ag85c_MPT51_HspX的重组卡介苗（rBCG-CMX）可诱导Th1和Th17反应，并比卡介苗提供更好的保护。研究表明，表达CMX也比卡介苗诱导出更好的保护效果，并且是一种强大的巨噬细胞激活剂。本研究的目的是评估重组CMX融合蛋白和rBCG-CMX对巨噬细胞的激活作用，并评估它们产生疫苗特异性免疫反应的能力。结果表明，卡介苗表达的rCMX蛋白（rBCG-CMX）可激活肺巨噬细胞；增加激活分子、细胞因子和MHC-II的表达。与rCMX的相互作用可激活转录因子NF-κB并诱导细胞因子TGF-β、TNF-α和IL-6的产生。对来自TLR-４或TLR-２基因敲除小鼠的骨髓来源巨噬细胞（BMM）的刺激表明，在没有TLR-4的情况下，不会产生IL-6。rBCG-CMX无法在TLR-4和TLR-2基因敲除小鼠中诱导CMX特异性Th1和Th17细胞，这表明这些受体参与了它们的诱导过程。我们得出结论，rBCG-CMX疫苗和rCMX蛋白均可激活巨噬细胞，并有利于该疫苗所需的特异性免疫反应。
