Role of T cells during the cerebral infection with Trypanosoma brucei

• Published in: PLoS neglected tropical diseases 2021-09, Vol.15 (9), p.e0009764-e0009764
• Main Authors: Olivera, Gabriela C, Vetter, Leonie, Tesoriero, Chiara, Del Gallo, Federico, Hedberg, Gustav, Basile, Juan, Rottenberg, Martin E
• Format: Article
• Language: English
• Subjects: 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; Medicin och hälsovetenskap; 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
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0009764

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 (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 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.