<italic toggle="yes">Ehrlichia chaffeensis</italic> and Its Invasin EtpE Block Reactive Oxygen Species Generation by Macrophages in a DNase X-Dependent Manner

ABSTRACT The obligatory intracellular pathogen Ehrlichia chaffeensis lacks most genes that confer resistance to oxidative stress but can block reactive oxygen species (ROS) generation by host monocytes-macrophages. Bacterial and host molecules responsible for this inhibition have not been identified...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Omid Teymournejad, Mingqun Lin, Yasuko Rikihisa
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	DNase X Ehrlichia EtpE macrophages neutrophils reactive oxygen species Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7ce7a015fa7d4051a4092c4cb8b618f5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7ce7a015fa7d4051a4092c4cb8b618f5
record_format	dspace
spelling	oai:doaj.org-article:7ce7a015fa7d4051a4092c4cb8b618f52021-11-15T15:51:55Z<italic toggle="yes">Ehrlichia chaffeensis</italic> and Its Invasin EtpE Block Reactive Oxygen Species Generation by Macrophages in a DNase X-Dependent Manner10.1128/mBio.01551-172150-7511https://doaj.org/article/7ce7a015fa7d4051a4092c4cb8b618f52017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01551-17https://doaj.org/toc/2150-7511ABSTRACT The obligatory intracellular pathogen Ehrlichia chaffeensis lacks most genes that confer resistance to oxidative stress but can block reactive oxygen species (ROS) generation by host monocytes-macrophages. Bacterial and host molecules responsible for this inhibition have not been identified. To infect host cells, Ehrlichia uses the C terminus of its surface invasin, entry-triggering protein of Ehrlichia (EtpE; EtpE-C), which directly binds the mammalian cell surface receptor glycosylphosphatidylinositol-anchored protein DNase X. We investigated whether EtpE-C binding to DNase X blocks ROS production by mouse bone marrow-derived macrophages (BMDMs). On the basis of a luminol-dependent chemiluminescence assay, E. chaffeensis inhibited phorbol myristate acetate (PMA)-induced ROS generation by BMDMs from wild-type, but not DNase X−/−, mice. EtpE-C is critical for inhibition, as recombinant EtpE-C (rEtpE-C)-coated latex beads, but not recombinant N-terminal EtpE-coated or uncoated beads, inhibited PMA-induced ROS generation by BMDMs from wild-type mice. DNase X is required for this inhibition, as none of these beads inhibited PMA-induced ROS generation by BMDMs from DNase X−/− mice. Previous studies showed that E. chaffeensis does not block ROS generation in neutrophils, a cell type that is a potent ROS generator but is not infected by E. chaffeensis. Human and mouse peripheral blood neutrophils did not express DNase X. Our findings point to a unique survival mechanism of ROS-sensitive obligate intramonocytic bacteria that involves invasin EtpE binding to DNase X on the host cell surface. This is the first report of bacterial invasin having such a subversive activity on ROS generation. IMPORTANCE Ehrlichia chaffeensis preferentially infects monocytes-macrophages and causes a life-threatening emerging tick-transmitted infectious disease called human monocytic ehrlichiosis. Ehrlichial infection, and hence the disease, depends on the ability of this bacterium to avoid or overcome powerful microbicidal mechanisms of host monocytes-macrophages, one of which is the generation of ROS. Our findings reveal that an ehrlichial surface invasin, EtpE, not only triggers bacterial entry but also blocks ROS generation by host macrophages through its host cell receptor, DNase X. As ROS sensitivity is an Achilles’ heel of this group of pathogens, understanding the mechanism by which E. chaffeensis rapidly blocks ROS generation suggests a new approach for developing effective anti-infective measures. The discovery of a ROS-blocking pathway is also important, as modulation of ROS generation is important in a variety of ailments and biological processes.Omid TeymournejadMingqun LinYasuko RikihisaAmerican Society for MicrobiologyarticleDNase XEhrlichiaEtpEmacrophagesneutrophilsreactive oxygen speciesMicrobiologyQR1-502ENmBio, Vol 8, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	DNase X Ehrlichia EtpE macrophages neutrophils reactive oxygen species Microbiology QR1-502
spellingShingle	DNase X Ehrlichia EtpE macrophages neutrophils reactive oxygen species Microbiology QR1-502 Omid Teymournejad Mingqun Lin Yasuko Rikihisa <italic toggle="yes">Ehrlichia chaffeensis</italic> and Its Invasin EtpE Block Reactive Oxygen Species Generation by Macrophages in a DNase X-Dependent Manner
description	ABSTRACT The obligatory intracellular pathogen Ehrlichia chaffeensis lacks most genes that confer resistance to oxidative stress but can block reactive oxygen species (ROS) generation by host monocytes-macrophages. Bacterial and host molecules responsible for this inhibition have not been identified. To infect host cells, Ehrlichia uses the C terminus of its surface invasin, entry-triggering protein of Ehrlichia (EtpE; EtpE-C), which directly binds the mammalian cell surface receptor glycosylphosphatidylinositol-anchored protein DNase X. We investigated whether EtpE-C binding to DNase X blocks ROS production by mouse bone marrow-derived macrophages (BMDMs). On the basis of a luminol-dependent chemiluminescence assay, E. chaffeensis inhibited phorbol myristate acetate (PMA)-induced ROS generation by BMDMs from wild-type, but not DNase X−/−, mice. EtpE-C is critical for inhibition, as recombinant EtpE-C (rEtpE-C)-coated latex beads, but not recombinant N-terminal EtpE-coated or uncoated beads, inhibited PMA-induced ROS generation by BMDMs from wild-type mice. DNase X is required for this inhibition, as none of these beads inhibited PMA-induced ROS generation by BMDMs from DNase X−/− mice. Previous studies showed that E. chaffeensis does not block ROS generation in neutrophils, a cell type that is a potent ROS generator but is not infected by E. chaffeensis. Human and mouse peripheral blood neutrophils did not express DNase X. Our findings point to a unique survival mechanism of ROS-sensitive obligate intramonocytic bacteria that involves invasin EtpE binding to DNase X on the host cell surface. This is the first report of bacterial invasin having such a subversive activity on ROS generation. IMPORTANCE Ehrlichia chaffeensis preferentially infects monocytes-macrophages and causes a life-threatening emerging tick-transmitted infectious disease called human monocytic ehrlichiosis. Ehrlichial infection, and hence the disease, depends on the ability of this bacterium to avoid or overcome powerful microbicidal mechanisms of host monocytes-macrophages, one of which is the generation of ROS. Our findings reveal that an ehrlichial surface invasin, EtpE, not only triggers bacterial entry but also blocks ROS generation by host macrophages through its host cell receptor, DNase X. As ROS sensitivity is an Achilles’ heel of this group of pathogens, understanding the mechanism by which E. chaffeensis rapidly blocks ROS generation suggests a new approach for developing effective anti-infective measures. The discovery of a ROS-blocking pathway is also important, as modulation of ROS generation is important in a variety of ailments and biological processes.
format	article
author	Omid Teymournejad Mingqun Lin Yasuko Rikihisa
author_facet	Omid Teymournejad Mingqun Lin Yasuko Rikihisa
author_sort	Omid Teymournejad
title	<italic toggle="yes">Ehrlichia chaffeensis</italic> and Its Invasin EtpE Block Reactive Oxygen Species Generation by Macrophages in a DNase X-Dependent Manner
title_short	<italic toggle="yes">Ehrlichia chaffeensis</italic> and Its Invasin EtpE Block Reactive Oxygen Species Generation by Macrophages in a DNase X-Dependent Manner
title_full	<italic toggle="yes">Ehrlichia chaffeensis</italic> and Its Invasin EtpE Block Reactive Oxygen Species Generation by Macrophages in a DNase X-Dependent Manner
title_fullStr	<italic toggle="yes">Ehrlichia chaffeensis</italic> and Its Invasin EtpE Block Reactive Oxygen Species Generation by Macrophages in a DNase X-Dependent Manner
title_full_unstemmed	<italic toggle="yes">Ehrlichia chaffeensis</italic> and Its Invasin EtpE Block Reactive Oxygen Species Generation by Macrophages in a DNase X-Dependent Manner
title_sort	<italic toggle="yes">ehrlichia chaffeensis</italic> and its invasin etpe block reactive oxygen species generation by macrophages in a dnase x-dependent manner
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/7ce7a015fa7d4051a4092c4cb8b618f5
work_keys_str_mv	AT omidteymournejad italictoggleyesehrlichiachaffeensisitalicanditsinvasinetpeblockreactiveoxygenspeciesgenerationbymacrophagesinadnasexdependentmanner AT mingqunlin italictoggleyesehrlichiachaffeensisitalicanditsinvasinetpeblockreactiveoxygenspeciesgenerationbymacrophagesinadnasexdependentmanner AT yasukorikihisa italictoggleyesehrlichiachaffeensisitalicanditsinvasinetpeblockreactiveoxygenspeciesgenerationbymacrophagesinadnasexdependentmanner
_version_	1718427346857361408

<italic toggle="yes">Ehrlichia chaffeensis</italic> and Its Invasin EtpE Block Reactive Oxygen Species Generation by Macrophages in a DNase X-Dependent Manner

Ejemplares similares