Meningeal macrophages protect against viral neuroinfection
Julie Rebejac
(1)
,
Elisa Eme-Scolan
(1, 2, 3)
,
Laurie Arnaud Paroutaud
(1)
,
Sarah Kharbouche
(1)
,
Matei Teleman
(1)
,
Lionel Spinelli
(1)
,
Emeline Gallo
(1)
,
Annie Roussel-Queval
(1)
,
Ana Zarubica
(4)
,
Amandine Sansoni
(4)
,
Quentin Bardin
(4)
,
Philippe Hoest
(4)
,
Marie-Cécile Michallet
(5)
,
Carine Brousse
(1)
,
Karine Crozat
(1)
,
Monica Manglani
(6)
,
Zhaoyuan Liu
(7)
,
Florent Ginhoux
(7, 8)
,
Dorian Mcgavern
(6)
,
Marc Dalod
(1)
,
Bernard Malissen
(1, 4)
,
Toby Lawrence
(1, 9)
,
Rejane Rua
(1)
1
CIML -
Centre d'Immunologie de Marseille - Luminy
2 ENS de Lyon - École normale supérieure de Lyon
3 UCBL - Université Claude Bernard Lyon 1
4 CIPHE - Centre d'Immunophénomique
5 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
6 NIH - National Institutes of Health [Bethesda, MD, USA]
7 Shanghai Jiao Tong University School of Medicine
8 ITIC - Immunologie anti-tumorale et immunothérapie des cancers
9 King‘s College London
2 ENS de Lyon - École normale supérieure de Lyon
3 UCBL - Université Claude Bernard Lyon 1
4 CIPHE - Centre d'Immunophénomique
5 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
6 NIH - National Institutes of Health [Bethesda, MD, USA]
7 Shanghai Jiao Tong University School of Medicine
8 ITIC - Immunologie anti-tumorale et immunothérapie des cancers
9 King‘s College London
Marie-Cécile Michallet
- Fonction : Auteur
- PersonId : 1012560
- IdHAL : mcmichallet
- ORCID : 0000-0001-5860-7460
- IdRef : 112569471
Marc Dalod
- Fonction : Auteur
- PersonId : 17179
- IdHAL : marc-dalod
- ORCID : 0000-0002-6436-7966
- IdRef : 151856427
Rejane Rua
- Fonction : Auteur
- PersonId : 737317
- IdHAL : rejane-rua
- ORCID : 0000-0002-4289-3498
- IdRef : 179412809
Résumé
The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II− MM were abundant neonatally, whereas MHC-II+ MM appeared over time. These barrier macrophages differentially responded to in vivo peripheral challenges such as LPS, SARS-CoV-2, and lymphocytic choriomeningitis virus (LCMV). Peripheral LCMV infection, which was asymptomatic, led to a transient infection and activation of the meninges. Mice lacking macrophages but conserving brain microglia, or mice bearing macrophage-specific deletion of Stat1 or Ifnar, exhibited extensive viral spread into the CNS. Transcranial pharmacological depletion strategies targeting MM locally resulted in several areas of the meninges becoming infected and fatal meningitis. Low numbers of MHC-II+ MM, which is seen upon LPS challenge or in neonates, corelated with higher viral load upon infection. Thus, MMs protect against viral infection and may present targets for therapeutic manipulation.
Format du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Résumé |
en
The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II− MM were abundant neonatally, whereas MHC-II+ MM appeared over time. These barrier macrophages differentially responded to in vivo peripheral challenges such as LPS, SARS-CoV-2, and lymphocytic choriomeningitis virus (LCMV). Peripheral LCMV infection, which was asymptomatic, led to a transient infection and activation of the meninges. Mice lacking macrophages but conserving brain microglia, or mice bearing macrophage-specific deletion of Stat1 or Ifnar, exhibited extensive viral spread into the CNS. Transcranial pharmacological depletion strategies targeting MM locally resulted in several areas of the meninges becoming infected and fatal meningitis. Low numbers of MHC-II+ MM, which is seen upon LPS challenge or in neonates, corelated with higher viral load upon infection. Thus, MMs protect against viral infection and may present targets for therapeutic manipulation.
|
Titre |
en
Meningeal macrophages protect against viral neuroinfection
|
Auteur(s) |
Julie Rebejac
1
, Elisa Eme-Scolan
1, 2, 3
, Laurie Arnaud Paroutaud
1
, Sarah Kharbouche
1
, Matei Teleman
1
, Lionel Spinelli
1
, Emeline Gallo
1
, Annie Roussel-Queval
1
, Ana Zarubica
4
, Amandine Sansoni
4
, Quentin Bardin
4
, Philippe Hoest
4
, Marie-Cécile Michallet
5
, Carine Brousse
1
, Karine Crozat
1
, Monica Manglani
6
, Zhaoyuan Liu
7
, Florent Ginhoux
7, 8
, Dorian Mcgavern
6
, Marc Dalod
1
, Bernard Malissen
1, 4
, Toby Lawrence
1, 9
, Rejane Rua
1
1
CIML -
Centre d'Immunologie de Marseille - Luminy
( 182245 )
- Parc scientifique et technologique de Luminy - 163, avenue de Luminy - Case 906 - 13288 Marseille cedex 09
- France
2
ENS de Lyon -
École normale supérieure de Lyon
( 6818 )
- 15 parvis René Descartes - BP 7000 - 69342 Lyon Cedex 07
- France
3
UCBL -
Université Claude Bernard Lyon 1
( 194495 )
- 43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex
- France
4
CIPHE -
Centre d'Immunophénomique
( 222359 )
- Parc Scientifique et Technologique de Luminy - 163 avenue de Luminy - Case 936 - 13288 Marseille Cedex 9
- France
5
UNICANCER/CRCL -
Centre de Recherche en Cancérologie de Lyon
( 139829 )
- 28, rue Laennec - 69373 Lyon
- France
6
NIH -
National Institutes of Health [Bethesda, MD, USA]
( 1182789 )
- 9000 Rockville Pike, Bethesda, Maryland 20892, USA
- États-Unis
7
Shanghai Jiao Tong University School of Medicine
( 305768 )
- 800 Dongchuan RD. Minhang District, Shanghai
- Chine
8
ITIC -
Immunologie anti-tumorale et immunothérapie des cancers
( 1041766 )
- 39 rue Camille Desmoulins, 94805, Villejuif cedex
- France
9
King‘s College London
( 327716 )
- Strand Campus, London WC2R 2LS
- Royaume-Uni
|
Date de publication |
2022
|
Date de publication électronique |
2022-11-01
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Volume |
55
|
Numéro |
11
|
Page/Identifiant |
2103-2117.e10
|
Langue du document |
Anglais
|
Audience |
Internationale
|
Domaine(s) |
|
Projet(s) ANR |
|
Mots-clés |
en
neuroinfection, LCMV, meninges, immunological barrier, macrophages, brain, virus, interferon
|
DOI | 10.1016/j.immuni.2022.10.005 |
Origine :
Fichiers produits par l'(les) auteur(s)
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