van Hooij Anouk, van Meijgaarden Krista E, Khatun Marufa, Soren Santosh, Walburg Kimberley, Alam Khorshed, Chowdhury Abu Sufian, van Hees Colette L M, Richardus Jan Hendrik, Geluk Annemieke
Deptartment of Infectious Diseases, LUCID, Leiden University Medical Center, the Netherlands.
Deptartment of Infectious Diseases, LUCID, Leiden University Medical Center, the Netherlands.
EBioMedicine. 2025 Jul 18;118:105855. doi: 10.1016/j.ebiom.2025.105855.
Leprosy is a debilitating, chronic infectious disease, ranking second after tuberculosis in the order of severe human mycobacterial diseases. If timely treatment is not initiated, infection with its causative agent, Mycobacterium leprae, can result in severe nerve damage leading to life-long disabilities. Host immunity largely dictates the spectral disease presentation, ranging from multi- to paucibacillary. Studying the host response to M. leprae is, however, complicated by the inability to culture this mycobacterium in vitro. Immune correlates of protection in persons at risk of leprosy are, therefore, essentially unknown.
To identify host factors related to mycobacterial control, functional mycobacterial growth inhibition assays combined with extensive immunophenotyping by spectral flow cytometry were performed for patients with leprosy and their contacts. This integrative approach merged sampling of peripheral blood mononuclear cells in low resource areas with immune-analysis using cutting edge technology.
In contrast to the current dogma, no intrinsic differences in mycobacterial control in vitro between patients with high and low bacillary loads were observed. Immunophenotyping at consecutive levels revealed a significant link between the induction of chemokines to mycobacterial antigens and expression of CXCR3 and CCR4 on adaptive immune cells in contacts controlling M. leprae infection.
These results offer more detailed insights into protective immunity against M. leprae and define host factors associated with bacterial control, fuelling improved diagnosis and treatment of leprosy.
Q.M. Gastmann-Wichers Foundation, the Leprosy Research Initiative & the Turing Foundation (ILEP#: 707.19.02), R2STOP; the Leprosy Mission Great Britain.
麻风病是一种使人衰弱的慢性传染病，在严重的人类分枝杆菌病中，其严重程度仅次于结核病。如果不及时开始治疗，感染其病原体麻风分枝杆菌会导致严重的神经损伤，从而造成终身残疾。宿主免疫在很大程度上决定了疾病谱的表现，从多菌型到少菌型。然而，由于无法在体外培养这种分枝杆菌，研究宿主对麻风分枝杆菌的反应变得复杂。因此，麻风病高危人群中保护作用的免疫相关因素基本上是未知的。
为了确定与分枝杆菌控制相关的宿主因素，对麻风病患者及其接触者进行了功能性分枝杆菌生长抑制试验，并结合光谱流式细胞术进行广泛的免疫表型分析。这种综合方法将低资源地区外周血单个核细胞的采样与使用前沿技术的免疫分析相结合。
与当前的观点相反，在体外分枝杆菌控制方面，未观察到高菌量和低菌量患者之间存在内在差异。连续水平的免疫表型分析显示，在控制麻风分枝杆菌感染的接触者中，趋化因子对分枝杆菌抗原的诱导与适应性免疫细胞上CXCR3和CCR4的表达之间存在显著联系。
这些结果为针对麻风分枝杆菌的保护性免疫提供了更详细的见解，并确定了与细菌控制相关的宿主因素，有助于改善麻风病的诊断和治疗。
Q.M. Gastmann-Wichers基金会、麻风病研究倡议组织和图灵基金会（ILEP#：707.19.02），R2STOP；英国麻风病传教团。
