Type I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.

Viral infections of central nervous system (CNS) often trigger inflammatory responses that give rise to a wide range of pathological outcomes. The CNS is equipped with an elaborate network of innate immune sentinels (e.g. microglia, macrophages, dendritic cells) that routinely serve as first respond...

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Autores principales:	Debasis Nayak, Kory R Johnson, Sara Heydari, Theodore L Roth, Bernd H Zinselmeyer, Dorian B McGavern
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a1d55c841b1a400d816d692518ceba79
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spelling	oai:doaj.org-article:a1d55c841b1a400d816d692518ceba792021-11-18T06:05:35ZType I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.1553-73661553-737410.1371/journal.ppat.1003395https://doaj.org/article/a1d55c841b1a400d816d692518ceba792013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23737750/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Viral infections of central nervous system (CNS) often trigger inflammatory responses that give rise to a wide range of pathological outcomes. The CNS is equipped with an elaborate network of innate immune sentinels (e.g. microglia, macrophages, dendritic cells) that routinely serve as first responders to these infections. The mechanisms that underlie the dynamic programming of these cells following CNS viral infection remain undefined. To gain insights into this programming, we utilized a combination of genomic and two-photon imaging approaches to study a pure innate immune response to a noncytopathic virus (lymphocytic choriomeningitis virus) as it established persistence in the brain. This enabled us to evaluate how global gene expression patterns were translated into myeloid cell dynamics following infection. Two-photon imaging studies revealed that innate myeloid cells mounted a vigorous early response to viral infection characterized by enhanced vascular patrolling and a complete morphological transformation. Interestingly, innate immune activity subsided over time and returned to a quasi-normal state as the virus established widespread persistence in the brain. At the genomic level, early myeloid cell dynamics were associated with massive changes in CNS gene expression, most of which declined over time and were linked to type I interferon signaling (IFN-I). Surprisingly, in the absence of IFN-I signaling, almost no differential gene expression was observed in the nervous system despite increased viral loads. In addition, two-photon imaging studies revealed that IFN-I receptor deficient myeloid cells were unresponsive to viral infection and remained in a naïve state. These data demonstrate that IFN-I engages non-redundant programming responsible for nearly all innate immune activity in the brain following a noncytopathic viral infection. This Achilles' heel could explain why so many neurotropic viruses have acquired strategies to suppress IFN-I.Debasis NayakKory R JohnsonSara HeydariTheodore L RothBernd H ZinselmeyerDorian B McGavernPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 5, p e1003395 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Debasis Nayak Kory R Johnson Sara Heydari Theodore L Roth Bernd H Zinselmeyer Dorian B McGavern Type I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.
description	Viral infections of central nervous system (CNS) often trigger inflammatory responses that give rise to a wide range of pathological outcomes. The CNS is equipped with an elaborate network of innate immune sentinels (e.g. microglia, macrophages, dendritic cells) that routinely serve as first responders to these infections. The mechanisms that underlie the dynamic programming of these cells following CNS viral infection remain undefined. To gain insights into this programming, we utilized a combination of genomic and two-photon imaging approaches to study a pure innate immune response to a noncytopathic virus (lymphocytic choriomeningitis virus) as it established persistence in the brain. This enabled us to evaluate how global gene expression patterns were translated into myeloid cell dynamics following infection. Two-photon imaging studies revealed that innate myeloid cells mounted a vigorous early response to viral infection characterized by enhanced vascular patrolling and a complete morphological transformation. Interestingly, innate immune activity subsided over time and returned to a quasi-normal state as the virus established widespread persistence in the brain. At the genomic level, early myeloid cell dynamics were associated with massive changes in CNS gene expression, most of which declined over time and were linked to type I interferon signaling (IFN-I). Surprisingly, in the absence of IFN-I signaling, almost no differential gene expression was observed in the nervous system despite increased viral loads. In addition, two-photon imaging studies revealed that IFN-I receptor deficient myeloid cells were unresponsive to viral infection and remained in a naïve state. These data demonstrate that IFN-I engages non-redundant programming responsible for nearly all innate immune activity in the brain following a noncytopathic viral infection. This Achilles' heel could explain why so many neurotropic viruses have acquired strategies to suppress IFN-I.
format	article
author	Debasis Nayak Kory R Johnson Sara Heydari Theodore L Roth Bernd H Zinselmeyer Dorian B McGavern
author_facet	Debasis Nayak Kory R Johnson Sara Heydari Theodore L Roth Bernd H Zinselmeyer Dorian B McGavern
author_sort	Debasis Nayak
title	Type I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.
title_short	Type I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.
title_full	Type I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.
title_fullStr	Type I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.
title_full_unstemmed	Type I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.
title_sort	type i interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a1d55c841b1a400d816d692518ceba79
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Type I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.

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