Antas Paulo R Z, da Silva Andreon S M, Albuquerque Lawrence H P, Almeida Matheus R, Pereira Evelyn N G S, Castello-Branco Luiz R R, de Ponte Carlos G G
Laboratório de Imunologia Clínica, Instituto Oswaldo Cruz, Fiocruz, and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Rio de Janeiro 21040-900, Brazil.
Department of Infectious Diseases, Leiden University Medical Centre, 2333ZA Leiden, The Netherlands.
Vaccines (Basel). 2022 Dec 30;11(1):86. doi: 10.3390/vaccines11010086.
Background: Tuberculosis (TB) is currently the second greatest killer worldwide and is caused by a single infectious agent. Since Bacillus Calmette−Guérin (BCG) is the only vaccine currently in use against TB, studies addressing the protective role of BCG in the context of inducible surface biomarkers are urgently required for TB control. Methods: In this study, groups of HIV-negative adult healthy donors (HD; n = 22) and neonate samples (UCB; n = 48) were voluntarily enrolled. The BCG Moreau strain was used for the in vitro mononuclear cell infections. Subsequently, phenotyping tools were used for surface biomarker detection. Monocytes were assayed for TLR4, B7-1, Dectin-1, EP2, and TIM-3 expression levels. Results: At 48 h, the BCG Moreau induced the highest TLR4, B7-1, and Dectin-1 levels in the HD group only (p-value < 0.05). TIM-3 expression failed to be modulated after BCG infection. At 72 h, BCG Moreau equally induced the highest EP2 levels in the HD group (p-value < 0.005), and higher levels were also found in HD when compared with the UCB group (p-value < 0.05). Conclusions: This study uncovers critical roles for biomarkers after the instruction of host monocyte activation patterns. Understanding the regulation of human innate immune responses is critical for vaccine development and for treating infectious diseases.
结核病（TB）目前是全球第二大致死病因，由单一传染源引起。由于卡介苗（BCG）是目前唯一用于预防结核病的疫苗，因此迫切需要开展在可诱导表面生物标志物背景下探讨卡介苗保护作用的研究，以控制结核病。方法：在本研究中，自愿招募了多组HIV阴性的成年健康供者（HD；n = 22）和新生儿样本（脐血；n = 48）。使用卡介苗莫罗菌株进行体外单核细胞感染。随后，使用表型分析工具检测表面生物标志物。检测单核细胞中TLR4、B7-1、Dectin-1、EP2和TIM-3的表达水平。结果：在48小时时，卡介苗莫罗菌株仅在HD组中诱导了最高的TLR4、B7-1和Dectin-1水平（p值<0.05）。卡介苗感染后TIM-3表达未被调节。在72小时时，卡介苗莫罗菌株同样在HD组中诱导了最高的EP2水平（p值<0.005），并且与脐血组相比，HD组中的EP2水平也更高（p值<0.05）。结论：本研究揭示了宿主单核细胞激活模式形成后生物标志物的关键作用。了解人类先天免疫反应的调节对于疫苗开发和治疗传染病至关重要。
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