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 predomina...

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Autores principales:	Gabriela C Olivera, Leonie Vetter, Chiara Tesoriero, Federico Del Gallo, Gustav Hedberg, Juan Basile, Martin E Rottenberg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/d02266cd13464e0ba538fe5733379b97
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spelling	oai:doaj.org-article:d02266cd13464e0ba538fe5733379b972021-12-02T20:24:00ZRole of T cells during the cerebral infection with Trypanosoma brucei.1935-27271935-273510.1371/journal.pntd.0009764https://doaj.org/article/d02266cd13464e0ba538fe5733379b972021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009764https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735The 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.Gabriela C OliveraLeonie VetterChiara TesorieroFederico Del GalloGustav HedbergJuan BasileMartin E RottenbergPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009764 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Gabriela C Olivera Leonie Vetter Chiara Tesoriero Federico Del Gallo Gustav Hedberg Juan Basile Martin E Rottenberg Role of T cells during the cerebral infection with Trypanosoma brucei.
description	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.
format	article
author	Gabriela C Olivera Leonie Vetter Chiara Tesoriero Federico Del Gallo Gustav Hedberg Juan Basile Martin E Rottenberg
author_facet	Gabriela C Olivera Leonie Vetter Chiara Tesoriero Federico Del Gallo Gustav Hedberg Juan Basile Martin E Rottenberg
author_sort	Gabriela C Olivera
title	Role of T cells during the cerebral infection with Trypanosoma brucei.
title_short	Role of T cells during the cerebral infection with Trypanosoma brucei.
title_full	Role of T cells during the cerebral infection with Trypanosoma brucei.
title_fullStr	Role of T cells during the cerebral infection with Trypanosoma brucei.
title_full_unstemmed	Role of T cells during the cerebral infection with Trypanosoma brucei.
title_sort	role of t cells during the cerebral infection with trypanosoma brucei.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d02266cd13464e0ba538fe5733379b97
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Role of T cells during the cerebral infection with Trypanosoma brucei.

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