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1.
Elife ; 72018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29582753

RESUMO

Giant viruses are ecologically important players in aquatic ecosystems that have challenged concepts of what constitutes a virus. Herein, we present the giant Bodo saltans virus (BsV), the first characterized representative of the most abundant group of giant viruses in ocean metagenomes, and the first isolate of a klosneuvirus, a subgroup of the Mimiviridae proposed from metagenomic data. BsV infects an ecologically important microzooplankton, the kinetoplastid Bodo saltans. Its 1.39 Mb genome encodes 1227 predicted ORFs, including a complex replication machinery. Yet, much of its translational apparatus has been lost, including all tRNAs. Essential genes are invaded by homing endonuclease-encoding self-splicing introns that may defend against competing viruses. Putative anti-host factors show extensive gene duplication via a genomic accordion indicating an ongoing evolutionary arms race and highlighting the rapid evolution and genomic plasticity that has led to genome gigantism and the enigma that is giant viruses.


Assuntos
Vírus Gigantes/isolamento & purificação , Kinetoplastida/virologia , Mimiviridae/isolamento & purificação , Água do Mar/virologia , Evolução Molecular , Genes Virais , Genoma Viral , Vírus Gigantes/classificação , Vírus Gigantes/genética , Interações Hospedeiro-Patógeno , Metagenômica , Mimiviridae/classificação , Mimiviridae/genética , Oceanos e Mares , Fases de Leitura Aberta
2.
J Immunol ; 195(2): 632-42, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-26085682

RESUMO

Although classical dendritic cells (DCs) arise from distinct progenitors in the bone marrow, the origin of inflammatory DCs and the distinction between monocyte-derived DCs and macrophages is less clear. In vitro culture of mouse bone marrow cells with GM-CSF is a well-established method to generate DCs, but GM-CSF has also been used to generate bone marrow-derived macrophages. In this article, we identify a distinct subpopulation of cells within the GM-CSF bone marrow-derived DC culture based on their ability to bind hyaluronan (HA), a major component of the extracellular matrix and ligand for CD44. HA identified a morphologically distinct subpopulation of cells within the immature DC population (CD11c(+) MHC II(mid/low)) that were CCR5(+)/CCR7(-) and proliferated in response to GM-CSF, but, unlike immature DCs, did not develop into mature DCs expressing CCR7 and high levels of MHC II, even after stimulation with LPS. The majority of these cells produced TNF-α in response to LPS but were unable to activate naive T cells, whereas the majority of mature DCs produced IL-12 and activated naive T cells. This HA binding population shared many characteristics with alveolar macrophages and was retained in the alveolar space after lung instillation even after LPS stimulation, whereas the MHC II(high) mature DCs were found in the draining lymph node. Thus, HA binding in combination with MHC II expression can be used to identify alveolar-like macrophages from GM-CSF-treated bone marrow cultures, which provides a useful in vitro model to study alveolar macrophages.


Assuntos
Células da Medula Óssea/citologia , Linhagem da Célula/imunologia , Células Dendríticas/citologia , Ácido Hialurônico/metabolismo , Macrófagos Alveolares/citologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Antígeno CD11c/genética , Antígeno CD11c/imunologia , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/imunologia , Ácido Hialurônico/farmacologia , Lipopolissacarídeos/farmacologia , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Linfonodos/citologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Ativação Linfocitária/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Cultura Primária de Células , Receptores CCR5/genética , Receptores CCR5/imunologia , Receptores CCR7/deficiência , Receptores CCR7/genética , Receptores CCR7/imunologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
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