Hertz David, Marwitz Sebastian, Eggers Lars, von Borstel Linda, Harikumar Parvathy Gishnu, Behrends Jochen, Jonigk Danny D, Manz Rudolf A, Goldmann Torsten, Schneider Bianca E
Host Determinants in Lung Infections, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Core Facility Histology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Front Immunol. 2025 Apr 7;16:1524500. doi: 10.3389/fimmu.2025.1524500. eCollection 2025.
Due to the historical dogma that host defense against intracellular pathogens is primarily mediated by cell-mediated immunity, B cells have long been considered unimportant in providing protection against (Mtb) and remained understudied for decades. However, emerging evidence highlights the multifaceted role of B cells in tuberculosis (TB) immunity. B cells accumulate at the site of infection in both animal models and human TB patients, suggesting a potential link to protective immunity. Still, the diverse roles of B cells in TB immunity are still being unraveled. In addition to producing antibodies, B cells secrete a wide range of cytokines that can influence the local immune response. In this study, we focused on the relevance of interleukin 10 (IL-10)-secreting B cells in the long-term control of the Beijing strain HN878.
B cell-specific IL-10 expression was assessed in IL-10 transcriptional reporter (Vert-X) mice following infection. To investigate the role of B cell-derived IL-10 in TB immunity, both male and female mice with a targeted knockout of IL-10 in B cells (IL-10/CD19) were infected with HN878. Disease progression, control of bacterial replication, and immunological changes were monitored throughout the course of infection.
B cells contribute to IL-10 production in the -infected lung in both sexes, with CD138 plasma cells serving as the primary source of B cell-derived IL-10. Mice lacking B cell-derived IL-10 exhibited increased resistance to aerosol infection, demonstrated by a delayed onset of clinical symptoms and prolonged survival. Notably, this effect was significantly more pronounced in males compared to females, and was associated with male-specific immune alterations.
Our research highlights a previously unrecognized sex-specific regulatory role of B cell-derived IL-10 during infection.
由于历史上的教条认为宿主对细胞内病原体的防御主要由细胞介导的免疫介导，长期以来，B细胞在提供针对结核分枝杆菌（Mtb）的保护方面一直被认为不重要，并且几十年来一直未得到充分研究。然而，新出现的证据凸显了B细胞在结核病（TB）免疫中的多方面作用。在动物模型和人类结核病患者中，B细胞都会在感染部位积聚，这表明其与保护性免疫存在潜在联系。尽管如此，B细胞在结核病免疫中的多种作用仍有待阐明。除了产生抗体外，B细胞还分泌多种可影响局部免疫反应的细胞因子。在本研究中，我们聚焦于分泌白细胞介素10（IL-10）的B细胞在长期控制北京株HN878中的相关性。
在感染结核分枝杆菌后，对IL-10转录报告基因（Vert-X）小鼠的B细胞特异性IL-10表达进行评估。为了研究B细胞衍生的IL-10在结核病免疫中的作用，对B细胞中IL-10靶向敲除的雄性和雌性小鼠（IL-10f/fCD19-Cre）感染结核分枝杆菌HN878。在整个感染过程中监测疾病进展、细菌复制的控制和免疫变化。
在感染结核分枝杆菌的两性小鼠肺中，B细胞都参与IL-10的产生，CD138浆细胞是B细胞衍生的IL-10的主要来源。缺乏B细胞衍生的IL-10的小鼠对气溶胶结核分枝杆菌感染表现出增强的抵抗力，临床症状出现延迟和存活时间延长证明了这一点。值得注意的是，这种效应在雄性小鼠中比在雌性小鼠中明显更显著，并且与雄性特异性免疫改变有关。
我们的研究突出了B细胞衍生的IL-10在结核分枝杆菌感染期间以前未被认识的性别特异性调节作用。
