The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic < i > Trypanosoma brucei < /i > infection

by Juan F. Quintana, Matthew C. Sinton, Praveena Chandrasegaran, Lalit Kumar Dubey, John Ogunsola, Moumen Al Samman, Michael Haley, Gail McConnell, Nono-Raymond Kuispond Swar, Dieudonn é Mumba Ngoyi, David Bending, Luis de Lecea, Annette MacLeod, Neil A. Mabbott The meningeal space is a critical brain structure providing immunosurveillance for the central nervous system (CNS), but the impact of infections on the meningeal immune landscape is far from being fully understood. The extracellular protozoan parasiteTrypanosoma brucei, which causes human African trypanosomiasis (HAT) or sleeping sickness, accumulates in the meningeal spaces, ultimately inducing severe meningitis and resulting in death if left untreated. Thus, sleeping sickness represents an attractive model to study immunological dynamics in the meninges during infection. Here, by combining single-cell transcriptomics and mass cytometry by time-of-flight (CyTOF) with in vivo interventions, we found that chronicT.brucei infection triggers the development of ectopic lymphoid aggregates (ELAs) in the murine meninges. These infection-induced ELAs were defined by the presence of ER-TR7+ fibroblastic reticular cells, CD21/35+ follicular dendritic cells (FDCs), CXCR5+ PD1+ T follicular helper-like phenotype, GL7+ CD95+ GC-like B cells, and plasmablasts/plasma cells. Furthermore, the B cells found in the infected meninges produced high-affinity autoantibodies able to recognise mouse brain antigens, in a process dependent ...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research