van Meijgaarden Krista E, Grace Patricia S, Wang Wenjun, Goletti Delia, Palmieri Fabrizio, Wuhrer Manfred, Ottenhoff Tom H M, Joosten Simone A
Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, the Netherlands.
Ragon Institute of MGH, MIT, and Harvard, Boston, MA, USA.
iScience. 2025 Apr 23;28(5):112504. doi: 10.1016/j.isci.2025.112504. eCollection 2025 May 16.
Tuberculosis (TB) remains a major cause of global mortality. Understanding the underlying immune response to the pathogen, , is essential for the development of vaccines. Evidence is accumulating supporting a contribution of innate immune cells and antibodies in control. Here, we focus on the functional capacity of antibodies from individuals with TB disease, both before and after TB treatment, individuals with TB infection, and healthy uninfected individuals, using an adapted mycobacterial growth inhibition assay, measuring Bacillus Calmette-Guérin BCG) growth inhibition. Sera displayed heterogeneous impact on mycobacterial growth control. This was correlated with enhanced phagocytic capacity, which was abrogated by blocking Fc receptors (FcR) and depletion of antibodies. This phenotype negatively associated with mono- and digalactosylated Fc-glycans of IgG. Together, we demonstrate disease state independent direct effects of sera to mycobacterial growth control and antibody-FcR interactions modulating phagocytic capacity.
结核病（TB）仍然是全球死亡的主要原因。了解对该病原体的潜在免疫反应对于疫苗开发至关重要。越来越多的证据支持先天性免疫细胞和抗体在控制中的作用。在这里，我们使用改良的分枝杆菌生长抑制试验，通过测量卡介苗（BCG）的生长抑制，重点研究结核病患者在治疗前后、结核感染个体以及健康未感染个体的抗体功能能力。血清对分枝杆菌生长控制呈现出异质性影响。这与增强的吞噬能力相关，而阻断Fc受体（FcR）和抗体耗竭可消除这种能力。这种表型与IgG的单半乳糖基化和双半乳糖基化Fc聚糖呈负相关。我们共同证明了血清对分枝杆菌生长控制的疾病状态无关的直接影响以及抗体-FcR相互作用对吞噬能力的调节作用。
