Role of meningeal lymphatic vessels in the T cell response against Toxoplasma gondii

Abstract

Abstract Toxoplasma gondii is an intracellular protozoan parasite that causes persistent infection in the central nervous system (CNS). Studies have demonstrated that continuous T cell recruitment to the brain is necessary for parasite control. However, the mechanisms by which T cell responses against T. gondii are maintained remain poorly understood. Recently, it was discovered that the meninges harbor a previously unappreciated lymphatic network that drains CNS protein and immune cells. We hypothesized that the meningeal lymphatic network is necessary for maintaining host-protective T cell responses against T. gondii. To test this hypothesis, we performed surgical ligation of the lymphatic vessels that carry cerebrospinal fluid via meningeal lymphatic vessels to the cervical lymph nodes. Following blockade of meningeal lymphatic outflow, we observed a decrease in the number and frequency of antigen-specific T cells in the deep cervical lymph nodes, supporting a role for meningeal lymphatic drainage in maintaining T cell responses against the parasite. We have also observed extensive lymphangiogenesis in the meninges during infection. Lymphangiogenesis has not previously been reported in response to CNS infection but could influence antigen or immune cell outflow from the CNS. Together, our results demonstrate that the meningeal lymphatic network dynamically responds to CNS infection with T. gondii and contributes to T cell responses against the parasite.