Splenic Transcriptional Responses in Severe Visceral Leishmaniasis: Impaired Leukocyte Chemotaxis and Cell Cycle Arrest

Structural changes in the spleen have been reported in several infectious diseases. In visceral leishmaniasis (VL), a severe parasitic disease caused by Leishmania spp., the loss of white pulp accompanies a severe clinical presentation. Hamster model reproduces aspects of human VL progression. In th...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Caroline Vilas Boas de Melo, Felipe Guimarães Torres, Micely D’El-Rei Hermida, Jonathan L. M. Fontes, Bianca Ramos Mesquita, Reginaldo Brito, Pablo Ivan P. Ramos, Gabriel R. Fernandes, Luiz Antônio Rodrigues Freitas, Ricardo Khouri, Carlos Henrique Nery Costa, Washington L. C. dos-Santos
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	visceral leishmanaisis white pulp remodeling spleen disorganization transcriptomic (RNA-Seq) spleen pathology hamster Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/4e144ad9b0484102a3c0edf2d8144b85
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4e144ad9b0484102a3c0edf2d8144b85
record_format	dspace
spelling	oai:doaj.org-article:4e144ad9b0484102a3c0edf2d8144b852021-11-05T12:35:00ZSplenic Transcriptional Responses in Severe Visceral Leishmaniasis: Impaired Leukocyte Chemotaxis and Cell Cycle Arrest1664-322410.3389/fimmu.2021.716314https://doaj.org/article/4e144ad9b0484102a3c0edf2d8144b852021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.716314/fullhttps://doaj.org/toc/1664-3224Structural changes in the spleen have been reported in several infectious diseases. In visceral leishmaniasis (VL), a severe parasitic disease caused by Leishmania spp., the loss of white pulp accompanies a severe clinical presentation. Hamster model reproduces aspects of human VL progression. In the early stages, a transcriptomic signature of leukocyte recruitment was associated with white pulp hyperplasia. Subsequently, impaired leukocyte chemotaxis with loss of T lymphocytes in the periarteriolar lymphoid sheath occurred. This differential gene expression was subsequently corroborated by transcriptomic profiling of spleens in severe human VL. At the latest stage, spleen disorganization was associated with increasing clinical signs of VL. White pulp disruption was accompanied by decreased DLK1 expression. The expression of CXCL13, CCR5, CCL19, CCR6, CCR7 and LTA decreased, likely regulated by CDKN2A overexpression. Our findings enlighten a pathway implying cell cycle arrest and decreased gene expression involved in spleen organization.Caroline Vilas Boas de MeloFelipe Guimarães TorresMicely D’El-Rei HermidaJonathan L. M. FontesBianca Ramos MesquitaReginaldo BritoPablo Ivan P. RamosGabriel R. FernandesLuiz Antônio Rodrigues FreitasRicardo KhouriCarlos Henrique Nery CostaWashington L. C. dos-SantosFrontiers Media S.A.articlevisceral leishmanaisiswhite pulp remodelingspleen disorganizationtranscriptomic (RNA-Seq)spleen pathologyhamsterImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	visceral leishmanaisis white pulp remodeling spleen disorganization transcriptomic (RNA-Seq) spleen pathology hamster Immunologic diseases. Allergy RC581-607
spellingShingle	visceral leishmanaisis white pulp remodeling spleen disorganization transcriptomic (RNA-Seq) spleen pathology hamster Immunologic diseases. Allergy RC581-607 Caroline Vilas Boas de Melo Felipe Guimarães Torres Micely D’El-Rei Hermida Jonathan L. M. Fontes Bianca Ramos Mesquita Reginaldo Brito Pablo Ivan P. Ramos Gabriel R. Fernandes Luiz Antônio Rodrigues Freitas Ricardo Khouri Carlos Henrique Nery Costa Washington L. C. dos-Santos Splenic Transcriptional Responses in Severe Visceral Leishmaniasis: Impaired Leukocyte Chemotaxis and Cell Cycle Arrest
description	Structural changes in the spleen have been reported in several infectious diseases. In visceral leishmaniasis (VL), a severe parasitic disease caused by Leishmania spp., the loss of white pulp accompanies a severe clinical presentation. Hamster model reproduces aspects of human VL progression. In the early stages, a transcriptomic signature of leukocyte recruitment was associated with white pulp hyperplasia. Subsequently, impaired leukocyte chemotaxis with loss of T lymphocytes in the periarteriolar lymphoid sheath occurred. This differential gene expression was subsequently corroborated by transcriptomic profiling of spleens in severe human VL. At the latest stage, spleen disorganization was associated with increasing clinical signs of VL. White pulp disruption was accompanied by decreased DLK1 expression. The expression of CXCL13, CCR5, CCL19, CCR6, CCR7 and LTA decreased, likely regulated by CDKN2A overexpression. Our findings enlighten a pathway implying cell cycle arrest and decreased gene expression involved in spleen organization.
format	article
author	Caroline Vilas Boas de Melo Felipe Guimarães Torres Micely D’El-Rei Hermida Jonathan L. M. Fontes Bianca Ramos Mesquita Reginaldo Brito Pablo Ivan P. Ramos Gabriel R. Fernandes Luiz Antônio Rodrigues Freitas Ricardo Khouri Carlos Henrique Nery Costa Washington L. C. dos-Santos
author_facet	Caroline Vilas Boas de Melo Felipe Guimarães Torres Micely D’El-Rei Hermida Jonathan L. M. Fontes Bianca Ramos Mesquita Reginaldo Brito Pablo Ivan P. Ramos Gabriel R. Fernandes Luiz Antônio Rodrigues Freitas Ricardo Khouri Carlos Henrique Nery Costa Washington L. C. dos-Santos
author_sort	Caroline Vilas Boas de Melo
title	Splenic Transcriptional Responses in Severe Visceral Leishmaniasis: Impaired Leukocyte Chemotaxis and Cell Cycle Arrest
title_short	Splenic Transcriptional Responses in Severe Visceral Leishmaniasis: Impaired Leukocyte Chemotaxis and Cell Cycle Arrest
title_full	Splenic Transcriptional Responses in Severe Visceral Leishmaniasis: Impaired Leukocyte Chemotaxis and Cell Cycle Arrest
title_fullStr	Splenic Transcriptional Responses in Severe Visceral Leishmaniasis: Impaired Leukocyte Chemotaxis and Cell Cycle Arrest
title_full_unstemmed	Splenic Transcriptional Responses in Severe Visceral Leishmaniasis: Impaired Leukocyte Chemotaxis and Cell Cycle Arrest
title_sort	splenic transcriptional responses in severe visceral leishmaniasis: impaired leukocyte chemotaxis and cell cycle arrest
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4e144ad9b0484102a3c0edf2d8144b85
work_keys_str_mv	AT carolinevilasboasdemelo splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT felipeguimaraestorres splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT micelydelreihermida splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT jonathanlmfontes splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT biancaramosmesquita splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT reginaldobrito splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT pabloivanpramos splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT gabrielrfernandes splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT luizantoniorodriguesfreitas splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT ricardokhouri splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT carloshenriquenerycosta splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest AT washingtonlcdossantos splenictranscriptionalresponsesinseverevisceralleishmaniasisimpairedleukocytechemotaxisandcellcyclearrest
_version_	1718444287760269312

Splenic Transcriptional Responses in Severe Visceral Leishmaniasis: Impaired Leukocyte Chemotaxis and Cell Cycle Arrest

Ejemplares similares