# The role of meningeal lymphatic vasculature in regulating immunity and intracranial pressure during central nervous system infection > **NIH NIH F30** · UNIVERSITY OF VIRGINIA · 2021 · $51,036 ## Abstract PROJECT SUMMARY Central nervous system (CNS) infections are a major cause of death and disability worldwide. Pathology results from tissue destruction and cerebral edema, which can lead to elevated intracranial pressure, a life-threatening emergency. Despite decades of research, it remains unclear how the adaptive immune system senses pathogens that have invaded the brain and how cerebral edema is resolved. These processes have been challenging to understand because the brain is devoid of lymphatic vessels, which in other tissues deliver antigen directly to lymph nodes for T cell priming and collect excess fluid that has accumulated as a result of inflammation, minimizing tissue swelling. Recently, however, Louveau et al. discovered a network of lymphatic vessels in the meninges that supports drainage of CNS fluid, protein, and immune cells to cervical lymph nodes. This groundbreaking discovery defines for the first time a route by which brain-derived antigen and fluid may be transported to lymph nodes for T cell priming and resolution of cerebral edema. Studies in this proposal will test the hypothesis that the meningeal lymphatic network regulates T cell immunity and intracranial pressure during CNS infection. CNS infection will be studied in mice using Toxoplasma gondii, a protozoan parasite that causes debilitating neurologic disease in immunocompromised individuals. In healthy hosts, chronic infection is asymptomatic due to a robust T. gondii-specific T cell response in the brain. Maintenance of the T cell response in the brain has been shown in mice to depend on continual antigen-specific T cell activation in the periphery. In Aim 1, we will test how meningeal lymphatic drainage affects host-protective T cell responses by blocking meningeal lymphatic outflow via surgical ligation of collecting vessels and measuring antigen-specific T cell responses in draining lymph nodes and brain. We will stain T cells for MHC tetramers specific for natural T. gondii antigen, and we will measure expression of Nur77-GFP, a specific reporter of TCR signaling, in OVA- specific T cells adoptively transferred to mice infected with an OVA-expressing strain of T. gondii. In our preliminary studies, we discovered significant growth of the meningeal lymphatic network during chronic infection, a process that has been found in other tissues to enhance fluid outflow during inflammation. Our lab has measured intracranial pressure (ICP) in infected mice and observed its magnitude to be increased prior to the onset of lymphangiogenesis and to have normalized after lymphangiogenesis has occurred. We will test the hypothesis in Aim 2 that meningeal lymphangiogenesis improves control of elevated intracranial pressure. We will inhibit lymphatic vessel growth using VEGFR-2 and -3 antagonists and perform fluid tracer studies, measurements of cerebral edema, and ICP tracing. Finally, we will assess whether induction of meningeal lymphangiogenesis by viral delivery of a VEGF-C ... ## Key facts - **NIH application ID:** 10232440 - **Project number:** 1F30AI154740-01A1 - **Recipient organization:** UNIVERSITY OF VIRGINIA - **Principal Investigator:** MICHAEL KOVACS - **Activity code:** F30 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2021 - **Award amount:** $51,036 - **Award type:** 1 - **Project period:** 2021-09-07 → — ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10232440 ## Citation > US National Institutes of Health, RePORTER application 10232440, The role of meningeal lymphatic vasculature in regulating immunity and intracranial pressure during central nervous system infection (1F30AI154740-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10232440. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*