Sousa Jorge, Martins Lívia Caricio, Moura Julia, Pereira Amanda, Vasconcelos Bárbara, Ferro Gustavo, Vasconcelos Pedro, Quaresma Juarez
Departamento de Patologia, Universidade do Estado do Pará, Belém 66050-540, Brazil.
Seção de Arbovirologia e Febres Hemorrágicas, Instituto Evandro Chagas, Ananindeua 67030-000, Brazil.
Int J Mol Sci. 2025 May 9;26(10):4522. doi: 10.3390/ijms26104522.
Tuberculosis (TB), caused by (Mtb), is a severe pulmonary disease with high mortality, particularly in low-income countries. Early diagnosis and timely treatment, including both intensive and maintenance phases, are critical for controlling the disease and preventing its transmission. In Brazil, where TB incidence remains high, thousands of new cases are reported annually. Transmission occurs primarily through airborne droplets expelled by infected individuals. The immune response involves various cell types, such as lymphocytes and macrophages, which form granulomas to limit the spread of the bacillus. Upon entering the lungs, Mtb is phagocytosed by immune cells, where it evades destruction by blocking phagolysosome formation and inhibiting phagosome acidification. In response, the immune system forms granulomas that contain the infection, although these can become reactivated if immune function deteriorates. Mtb also interferes with host cellular organelles, particularly the endoplasmic reticulum (ER) and mitochondria, inducing cellular stress and apoptosis, which aids in its survival. Key Mtb-secreted proteins, such as BAG2 and CdhM, modulate autophagy and apoptosis pathways, influencing pathogen survival within immune cells. A deeper understanding of these molecular mechanisms, particularly the role of ER stress and its impact on immune responses, is essential for developing novel therapeutic strategies for TB prevention and treatment.
由结核分枝杆菌（Mtb）引起的结核病（TB）是一种严重的肺部疾病，死亡率很高，在低收入国家尤为如此。早期诊断和及时治疗，包括强化期和维持期，对于控制疾病和防止其传播至关重要。在结核病发病率仍然很高的巴西，每年报告数千例新病例。传播主要通过受感染个体咳出的空气传播飞沫发生。免疫反应涉及多种细胞类型，如淋巴细胞和巨噬细胞，它们形成肉芽肿以限制杆菌的传播。进入肺部后，Mtb被免疫细胞吞噬，在那里它通过阻断吞噬溶酶体的形成和抑制吞噬体酸化来逃避破坏。作为回应，免疫系统形成包含感染的肉芽肿，尽管如果免疫功能恶化，这些肉芽肿可能会重新激活。Mtb还会干扰宿主细胞细胞器，特别是内质网（ER）和线粒体，诱导细胞应激和细胞凋亡，这有助于其生存。关键的Mtb分泌蛋白，如BAG2和CdhM，调节自噬和凋亡途径，影响病原体在免疫细胞内的生存。深入了解这些分子机制，特别是内质网应激的作用及其对免疫反应的影响，对于开发预防和治疗结核病的新治疗策略至关重要。
