ROLE OF T CELLS DURING THE CEREBRAL INFECTION WITH TRYPANOSOMA BRUCEI.

Role of T cells during the cerebral infection with Trypanosoma brucei.

Role of T cells during the cerebral infection with Trypanosoma brucei.

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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 bundle cells, whereas, during the encephalitic stage T cells acquired a tissue resident memory phenotype (TRM) 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 Ice Cream Dippers 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 TRM 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.

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