MAVS signaling shapes microglia responses to neurotropic virus infection

Abstract Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs−/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Gern, Olivia Luise [verfasserIn] Pavlou, Andreas [verfasserIn] Mulenge, Felix [verfasserIn] Busker, Lena Mareike [verfasserIn] Ghita, Luca [verfasserIn] Aringo, Angela [verfasserIn] Costa, Bibiana [verfasserIn] Spanier, Julia [verfasserIn] Waltl, Inken [verfasserIn] Stangel, Martin [verfasserIn] Kalinke, Ulrich [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	Microglia MAVS IPS-1 VISA Cardif Virus CNS

Anmerkung:	© The Author(s) 2024

Übergeordnetes Werk:	Enthalten in: Journal of neuroinflammation - BioMed Central, 2004, 21(2024), 1 vom: 18. Okt.
Übergeordnetes Werk:	volume:21 ; year:2024 ; number:1 ; day:18 ; month:10

Links:	Volltext

DOI / URN:	10.1186/s12974-024-03258-6

Katalog-ID:	SPR057886318

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allfields	10.1186/s12974-024-03258-6 doi (DE-627)SPR057886318 (SPR)s12974-024-03258-6-e DE-627 ger DE-627 rakwb eng 610 VZ Gern, Olivia Luise verfasserin aut MAVS signaling shapes microglia responses to neurotropic virus infection 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs−/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS. Microglia (dpeaa)DE-He213 MAVS (dpeaa)DE-He213 IPS-1 (dpeaa)DE-He213 VISA (dpeaa)DE-He213 Cardif (dpeaa)DE-He213 Virus (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Pavlou, Andreas verfasserin aut Mulenge, Felix verfasserin aut Busker, Lena Mareike verfasserin aut Ghita, Luca verfasserin aut Aringo, Angela verfasserin aut Costa, Bibiana verfasserin aut Spanier, Julia verfasserin aut Waltl, Inken verfasserin aut Stangel, Martin verfasserin aut Kalinke, Ulrich verfasserin aut Enthalten in Journal of neuroinflammation BioMed Central, 2004 21(2024), 1 vom: 18. Okt. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:21 year:2024 number:1 day:18 month:10 https://dx.doi.org/10.1186/s12974-024-03258-6 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2024 1 18 10
spelling	10.1186/s12974-024-03258-6 doi (DE-627)SPR057886318 (SPR)s12974-024-03258-6-e DE-627 ger DE-627 rakwb eng 610 VZ Gern, Olivia Luise verfasserin aut MAVS signaling shapes microglia responses to neurotropic virus infection 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs−/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS. Microglia (dpeaa)DE-He213 MAVS (dpeaa)DE-He213 IPS-1 (dpeaa)DE-He213 VISA (dpeaa)DE-He213 Cardif (dpeaa)DE-He213 Virus (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Pavlou, Andreas verfasserin aut Mulenge, Felix verfasserin aut Busker, Lena Mareike verfasserin aut Ghita, Luca verfasserin aut Aringo, Angela verfasserin aut Costa, Bibiana verfasserin aut Spanier, Julia verfasserin aut Waltl, Inken verfasserin aut Stangel, Martin verfasserin aut Kalinke, Ulrich verfasserin aut Enthalten in Journal of neuroinflammation BioMed Central, 2004 21(2024), 1 vom: 18. Okt. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:21 year:2024 number:1 day:18 month:10 https://dx.doi.org/10.1186/s12974-024-03258-6 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2024 1 18 10
allfields_unstemmed	10.1186/s12974-024-03258-6 doi (DE-627)SPR057886318 (SPR)s12974-024-03258-6-e DE-627 ger DE-627 rakwb eng 610 VZ Gern, Olivia Luise verfasserin aut MAVS signaling shapes microglia responses to neurotropic virus infection 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs−/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS. Microglia (dpeaa)DE-He213 MAVS (dpeaa)DE-He213 IPS-1 (dpeaa)DE-He213 VISA (dpeaa)DE-He213 Cardif (dpeaa)DE-He213 Virus (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Pavlou, Andreas verfasserin aut Mulenge, Felix verfasserin aut Busker, Lena Mareike verfasserin aut Ghita, Luca verfasserin aut Aringo, Angela verfasserin aut Costa, Bibiana verfasserin aut Spanier, Julia verfasserin aut Waltl, Inken verfasserin aut Stangel, Martin verfasserin aut Kalinke, Ulrich verfasserin aut Enthalten in Journal of neuroinflammation BioMed Central, 2004 21(2024), 1 vom: 18. Okt. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:21 year:2024 number:1 day:18 month:10 https://dx.doi.org/10.1186/s12974-024-03258-6 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2024 1 18 10
allfieldsGer	10.1186/s12974-024-03258-6 doi (DE-627)SPR057886318 (SPR)s12974-024-03258-6-e DE-627 ger DE-627 rakwb eng 610 VZ Gern, Olivia Luise verfasserin aut MAVS signaling shapes microglia responses to neurotropic virus infection 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs−/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS. Microglia (dpeaa)DE-He213 MAVS (dpeaa)DE-He213 IPS-1 (dpeaa)DE-He213 VISA (dpeaa)DE-He213 Cardif (dpeaa)DE-He213 Virus (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Pavlou, Andreas verfasserin aut Mulenge, Felix verfasserin aut Busker, Lena Mareike verfasserin aut Ghita, Luca verfasserin aut Aringo, Angela verfasserin aut Costa, Bibiana verfasserin aut Spanier, Julia verfasserin aut Waltl, Inken verfasserin aut Stangel, Martin verfasserin aut Kalinke, Ulrich verfasserin aut Enthalten in Journal of neuroinflammation BioMed Central, 2004 21(2024), 1 vom: 18. Okt. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:21 year:2024 number:1 day:18 month:10 https://dx.doi.org/10.1186/s12974-024-03258-6 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2024 1 18 10
allfieldsSound	10.1186/s12974-024-03258-6 doi (DE-627)SPR057886318 (SPR)s12974-024-03258-6-e DE-627 ger DE-627 rakwb eng 610 VZ Gern, Olivia Luise verfasserin aut MAVS signaling shapes microglia responses to neurotropic virus infection 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Abstract Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs−/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS. Microglia (dpeaa)DE-He213 MAVS (dpeaa)DE-He213 IPS-1 (dpeaa)DE-He213 VISA (dpeaa)DE-He213 Cardif (dpeaa)DE-He213 Virus (dpeaa)DE-He213 CNS (dpeaa)DE-He213 Pavlou, Andreas verfasserin aut Mulenge, Felix verfasserin aut Busker, Lena Mareike verfasserin aut Ghita, Luca verfasserin aut Aringo, Angela verfasserin aut Costa, Bibiana verfasserin aut Spanier, Julia verfasserin aut Waltl, Inken verfasserin aut Stangel, Martin verfasserin aut Kalinke, Ulrich verfasserin aut Enthalten in Journal of neuroinflammation BioMed Central, 2004 21(2024), 1 vom: 18. Okt. (DE-627)391784781 (DE-600)2156455-3 1742-2094 nnns volume:21 year:2024 number:1 day:18 month:10 https://dx.doi.org/10.1186/s12974-024-03258-6 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2024 1 18 10
language	English
source	Enthalten in Journal of neuroinflammation 21(2024), 1 vom: 18. Okt. volume:21 year:2024 number:1 day:18 month:10
sourceStr	Enthalten in Journal of neuroinflammation 21(2024), 1 vom: 18. Okt. volume:21 year:2024 number:1 day:18 month:10
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Microglia MAVS IPS-1 VISA Cardif Virus CNS
dewey-raw	610
isfreeaccess_bool	true
container_title	Journal of neuroinflammation
authorswithroles_txt_mv	Gern, Olivia Luise @@aut@@ Pavlou, Andreas @@aut@@ Mulenge, Felix @@aut@@ Busker, Lena Mareike @@aut@@ Ghita, Luca @@aut@@ Aringo, Angela @@aut@@ Costa, Bibiana @@aut@@ Spanier, Julia @@aut@@ Waltl, Inken @@aut@@ Stangel, Martin @@aut@@ Kalinke, Ulrich @@aut@@
publishDateDaySort_date	2024-10-18T00:00:00Z
hierarchy_top_id	391784781
dewey-sort	3610
id	SPR057886318
language_de	englisch
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author	Gern, Olivia Luise
spellingShingle	Gern, Olivia Luise ddc 610 misc Microglia misc MAVS misc IPS-1 misc VISA misc Cardif misc Virus misc CNS MAVS signaling shapes microglia responses to neurotropic virus infection
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topic_title	610 VZ MAVS signaling shapes microglia responses to neurotropic virus infection Microglia (dpeaa)DE-He213 MAVS (dpeaa)DE-He213 IPS-1 (dpeaa)DE-He213 VISA (dpeaa)DE-He213 Cardif (dpeaa)DE-He213 Virus (dpeaa)DE-He213 CNS (dpeaa)DE-He213
topic	ddc 610 misc Microglia misc MAVS misc IPS-1 misc VISA misc Cardif misc Virus misc CNS
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title	MAVS signaling shapes microglia responses to neurotropic virus infection
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title_full	MAVS signaling shapes microglia responses to neurotropic virus infection
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author_browse	Gern, Olivia Luise Pavlou, Andreas Mulenge, Felix Busker, Lena Mareike Ghita, Luca Aringo, Angela Costa, Bibiana Spanier, Julia Waltl, Inken Stangel, Martin Kalinke, Ulrich
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title_sort	mavs signaling shapes microglia responses to neurotropic virus infection
title_auth	MAVS signaling shapes microglia responses to neurotropic virus infection
abstract	Abstract Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs−/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS. © The Author(s) 2024
abstractGer	Abstract Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs−/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS. © The Author(s) 2024
abstract_unstemmed	Abstract Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs−/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS. © The Author(s) 2024
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title_short	MAVS signaling shapes microglia responses to neurotropic virus infection
url	https://dx.doi.org/10.1186/s12974-024-03258-6
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author2	Pavlou, Andreas Mulenge, Felix Busker, Lena Mareike Ghita, Luca Aringo, Angela Costa, Bibiana Spanier, Julia Waltl, Inken Stangel, Martin Kalinke, Ulrich
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