Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection

ABSTRACT Coronaviruses efficiently inhibit interferon (IFN) induction in nonhematopoietic cells and conventional dendritic cells (cDC). However, IFN is produced in infected macrophages, microglia, and plasmacytoid dendritic cells (pDC). To begin to understand why IFN is produced in infected macropha...

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Autores principales:	Haixia Zhou, Jincun Zhao, Stanley Perlman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2010
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/13435731e03046f8a3daa1cda50741b6
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spelling	oai:doaj.org-article:13435731e03046f8a3daa1cda50741b62021-11-15T15:38:15ZAutocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection10.1128/mBio.00219-102150-7511https://doaj.org/article/13435731e03046f8a3daa1cda50741b62010-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00219-10https://doaj.org/toc/2150-7511ABSTRACT Coronaviruses efficiently inhibit interferon (IFN) induction in nonhematopoietic cells and conventional dendritic cells (cDC). However, IFN is produced in infected macrophages, microglia, and plasmacytoid dendritic cells (pDC). To begin to understand why IFN is produced in infected macrophages, we infected bone marrow-derived macrophages (BMM) and as a control, bone marrow-derived DC (BMDC) with the coronavirus mouse hepatitis virus (MHV). As expected, BMM but not BMDC expressed type I IFN. IFN production in infected BMM was nearly completely dependent on signaling through the alpha/beta interferon (IFN-α/β) receptor (IFNAR). Several IFN-dependent cytokines and chemokines showed the same expression pattern, with enhanced production in BMM compared to BMDC and dependence upon signaling through the IFNAR. Exogenous IFN enhanced IFN-dependent gene expression in BMM at early times after infection and in BMDC at all times after infection but did not stimulate expression of molecules that signal through myeloid differentiation factor 88 (MyD88), such as tumor necrosis factor (TNF). Collectively, our results show that IFN is produced at early times postinfection (p.i.) in MHV-infected BMM, but not in BMDC, and primes expression of IFN and IFN-responsive genes. Further, our results also show that BMM are generally more responsive to MHV infection, since MyD88-dependent pathways are also activated to a greater extent in these cells than in BMDC. IMPORTANCE Coronaviruses cause diseases with various degrees of severity in humans, including severe acute respiratory syndrome (SARS). In domestic and companion animals, coronaviruses induce interferon (IFN) in only a few cell types. In particular, macrophages, which are known to have both protective and pathogenic roles in coronavirus infections, express IFN while dendritic cells do not. Little is known about the basis of these cell-specific differences in IFN induction. Here, we show that an animal coronavirus, mouse hepatitis virus, induces IFN and other IFN-responsive molecules in macrophages, but not in dendritic cells, via a feedback loop that is dependent upon low-level IFN expression at early times after infection. This pathway of cellular activation may be a useful target for modulating macrophage function in order to selectively enhance the antivirus immune response and diminish the pathogenic role of these cells in SARS and other coronavirus infections.Haixia ZhouJincun ZhaoStanley PerlmanAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 1, Iss 4 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Haixia Zhou Jincun Zhao Stanley Perlman Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection
description	ABSTRACT Coronaviruses efficiently inhibit interferon (IFN) induction in nonhematopoietic cells and conventional dendritic cells (cDC). However, IFN is produced in infected macrophages, microglia, and plasmacytoid dendritic cells (pDC). To begin to understand why IFN is produced in infected macrophages, we infected bone marrow-derived macrophages (BMM) and as a control, bone marrow-derived DC (BMDC) with the coronavirus mouse hepatitis virus (MHV). As expected, BMM but not BMDC expressed type I IFN. IFN production in infected BMM was nearly completely dependent on signaling through the alpha/beta interferon (IFN-α/β) receptor (IFNAR). Several IFN-dependent cytokines and chemokines showed the same expression pattern, with enhanced production in BMM compared to BMDC and dependence upon signaling through the IFNAR. Exogenous IFN enhanced IFN-dependent gene expression in BMM at early times after infection and in BMDC at all times after infection but did not stimulate expression of molecules that signal through myeloid differentiation factor 88 (MyD88), such as tumor necrosis factor (TNF). Collectively, our results show that IFN is produced at early times postinfection (p.i.) in MHV-infected BMM, but not in BMDC, and primes expression of IFN and IFN-responsive genes. Further, our results also show that BMM are generally more responsive to MHV infection, since MyD88-dependent pathways are also activated to a greater extent in these cells than in BMDC. IMPORTANCE Coronaviruses cause diseases with various degrees of severity in humans, including severe acute respiratory syndrome (SARS). In domestic and companion animals, coronaviruses induce interferon (IFN) in only a few cell types. In particular, macrophages, which are known to have both protective and pathogenic roles in coronavirus infections, express IFN while dendritic cells do not. Little is known about the basis of these cell-specific differences in IFN induction. Here, we show that an animal coronavirus, mouse hepatitis virus, induces IFN and other IFN-responsive molecules in macrophages, but not in dendritic cells, via a feedback loop that is dependent upon low-level IFN expression at early times after infection. This pathway of cellular activation may be a useful target for modulating macrophage function in order to selectively enhance the antivirus immune response and diminish the pathogenic role of these cells in SARS and other coronavirus infections.
format	article
author	Haixia Zhou Jincun Zhao Stanley Perlman
author_facet	Haixia Zhou Jincun Zhao Stanley Perlman
author_sort	Haixia Zhou
title	Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection
title_short	Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection
title_full	Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection
title_fullStr	Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection
title_full_unstemmed	Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection
title_sort	autocrine interferon priming in macrophages but not dendritic cells results in enhanced cytokine and chemokine production after coronavirus infection
publisher	American Society for Microbiology
publishDate	2010
url	https://doaj.org/article/13435731e03046f8a3daa1cda50741b6
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Autocrine Interferon Priming in Macrophages but Not Dendritic Cells Results in Enhanced Cytokine and Chemokine Production after Coronavirus Infection

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