Identification of IL-10 producing T cells in CSF and blood during treatment of subarachnoid neurocysticercosis
Neurocysticercosis (NCC) is a parasitic infection that affects the central nervous system and is increasingly found in patients in non-endemic regions. Subarachnoid neurocysticercosis (SANCC) is the most severe form of this disease and is largely responsible for mortality associated with NCC. Inflammation is often an important factor in the treatment of SANCC as overactivity can lead to serious complications, but suppression induced by anti-inflammatory molecules – namely interleukin 10 (IL-10) – can lead to an increased time to cure. To better understand the local inflammatory milieu associated with SANCC, we performed single cell RNA sequencing to achieve an unbiased profile of immune cell populations in the cerebrospinal fluid (CSF), and we used flow cytometry to identify important producers of IL-10 in the CSF and blood. These analyses revealed a diverse combination of immune cell populations within the CSF including multiple myeloid and lymphoid populations. We identified three primary sources of IL-10 in CSF – natural regulatory T cells (nTregs), induced regulatory T cells (iTregs), and Th17 cells – with iTregs being the single largest contributor in this compartment. Our data also show that these populations – and the abundance of IL-10 producing CD4+ T cells as a whole – differed between CSF and blood. Interestingly, these IL-10 producing nTregs, iTregs, and Th17 cells persist in the CSF over the course of SANCC treatment, indicating that immunosuppression within the central nervous system is unaffected despite decreases in parasite antigen over time. Overall, this study deepens our understanding of the suppressive phenotype that deters SANCC treatment success and provides a comprehensive blueprint of the local and systemic immunology associated with this important disease process. Overall design: These are cerebrospinal fluid samples collected from patients treated at the NIH for subarachnoid neurocysticercosis. All patients provided two samples from different timepoints during anthelmintic treatment.