Role of T cells during the cerebral infection with Trypanosoma brucei

The infection by Trypanosoma brucei brucei ( T . b . b .), a protozoan parasite, is characterized by an early-systemic stage followed by a late stage in which parasites invade the brain parenchyma in a T cell-dependent manner. Here we found that early after infection effector-memory T cells were predominant among brain T cells, whereas, during the encephalitic stage T cells acquired a tissue resident memory phenotype (T RM ) and expressed PD1. Both CD4 and CD8 T cells were independently redundant for the penetration of T . b . b . and other leukocytes into the brain parenchyma. The role of lymphoid cells during the T . b . b . infection was studied by comparing T- and B-cell deficient rag1 -/- and WT mice. Early after infection, parasites located in circumventricular organs, brain structures with increased vascular permeability, particularly in the median eminence (ME), paced closed to the sleep-wake regulatory arcuate nucleus of the hypothalamus (Arc). Whereas parasite levels in the ME were higher in rag1 -/- than in WT mice, leukocytes were instead reduced. Rag1 -/- infected mice showed increased levels of meca32 mRNA coding for a blood /hypothalamus endothelial molecule absent in the blood-brain-barrier (BBB). Both immune and metabolic transcripts were elevated in the ME/Arc of WT and rag1 -/- mice early after infection, except for ifng mRNA, which levels were only increased in WT mice. Finally, using a non-invasive sleep-wake cycle assessment method we proposed a putative role of lymphocytes in mediating sleep alterations during the infection with T . b . b . Thus, the majority of T cells in the brain during the early stage of T . b . b . infection expressed an effector-memory phenotype while T RM cells developed in the late stage of infection. T cells and parasites invade the ME/Arc altering the metabolic and inflammatory responses during the early stage of infection and modulating sleep disturbances.