Journal Article

Role of T cells during the cerebral infection with Trypanosoma brucei

Hedberg, Gustav, Vetter, Leonie, Tesoriero, Chiara, Basile, Juan, Olivera, Gabriela C., Del Gallo, Federico, Rottenberg, Martin E.

2021

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: African trypanosomiasis / Animals / Arcuate nucleus / Biology and Life Sciences / Blood / Blood-brain barrier / Body organs / Brain / Brain - parasitology / Care and treatment / CD4 antigen / CD8 antigen / Cells / Central Nervous System Diseases - immunology / Central Nervous System Diseases - parasitology / Coding / Diagnosis / Dosage and administration / Effector cells / Genotype & phenotype / Homeodomain Proteins - genetics / Homeodomain Proteins - metabolism / Humans / Hypothalamus / Identification and classification / Immunologic Memory / Immunological memory / Infections / Inflammation / Leukocytes / Levels / Lymphatic system / Lymphocytes / Lymphocytes B / Lymphocytes T / Lymphoid cells / Medicine and Health Sciences / Memory cells / Mice / Mice, Knockout / Neural coding / Observations / Organs / Parasites / Parenchyma / PD-1 protein / Permeability / Phenotypes / Protozoa / RAG1 protein / Sleep / Sleep and wakefulness / Suramin sodium / T cells / T-Lymphocyte Subsets - physiology / Tropical diseases / Trypanosoma brucei / Trypanosoma brucei brucei / Trypanosomiasis, African - immunology / Trypanosomiasis, African - pathology / Tumor necrosis factor-TNF / Viral infections