Tavares-Gomes Leticia, Polidori Margherita, Monney Camille, Neuhaus Géraldine, Vidondo Beatriz, Witz Guillaume, Hemphill Andrew, Oevermann Anna
Division of Neurological Sciences, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
Acta Neuropathol. 2025 Jun 16;149(1):63. doi: 10.1007/s00401-025-02900-8.
Bacterial infections of the central nervous system (CNS) pose a significant threat to public health, especially with the growing challenge of antimicrobial resistance. Among these, Listeria monocytogenes (Lm) stands out as a key pathogen, responsible for often fatal neurolisteriosis in humans and cattle. Emerging evidence highlights the distinct roles played by microglia, the resident macrophages of the CNS, and infiltrating monocyte-derived macrophages (MDM) during neuroinflammation. Using bovine models, we investigated the interactions between these two macrophage populations and Lm during infection. Our results show that Lm thrives in the cytosol of microglia, driving productive infection and facilitating bacterial spread. In contrast, MDM effectively sequesters Lm within the phagolysosomal system, limiting its replication and inducing a viable but non-culturable (VBNC) state without completely eliminating the pathogen. Listeriolysin O contributes to the dichotomy of Lm fate, determining whether Lm escapes into the cytosol or transitions to the VBNC state. These findings underscore the complexity of Lm-host dynamics in neurolisteriosis, emphasizing the distinct yet complementary roles of microglia and MDM in shaping CNS infection. By elucidating these mechanisms, our study offers new perspectives on the neurolisteriosis pathogenesis and opens avenues for innovative therapeutic approaches to combat bacterial neuroinfections.
中枢神经系统（CNS）的细菌感染对公众健康构成重大威胁，尤其是在抗菌药物耐药性挑战日益严峻的情况下。其中，单核细胞增生李斯特菌（Lm）是一种关键病原体，可导致人类和牛群中常致命的神经李斯特菌病。新出现的证据凸显了小胶质细胞（中枢神经系统的常驻巨噬细胞）和浸润的单核细胞衍生巨噬细胞（MDM）在神经炎症过程中发挥的不同作用。我们使用牛模型研究了这两种巨噬细胞群体与感染期间的Lm之间的相互作用。我们的结果表明，Lm在小胶质细胞的胞质溶胶中茁壮成长，引发有效感染并促进细菌传播。相比之下，MDM有效地将Lm隔离在吞噬溶酶体系统内，限制其复制并诱导其进入活的但不可培养（VBNC）状态，而不会完全消除病原体。溶血素O导致了Lm命运的二分法，决定了Lm是逃逸到胞质溶胶中还是转变为VBNC状态。这些发现强调了神经李斯特菌病中Lm与宿主相互作用的复杂性，强调了小胶质细胞和MDM在塑造中枢神经系统感染方面独特但互补的作用。通过阐明这些机制，我们的研究为神经李斯特菌病的发病机制提供了新的视角，并为对抗细菌性神经感染的创新治疗方法开辟了道路。
