Meningeal macrophages protect against viral neuroinfection

Rebejac, Julie; Eme‐Scolan, Elisa; Paroutaud, Laurie Arnaud; Kharbouche, Sarah; Teleman, Matei; Spinelli, Lionel; Gallo, Emeline; Roussel‐Queval, Annie; Zarubica, Ana; Sansoni, Amandine; Bardin, Quentin; Hoest, Philippe; Michallet, M; Brousse, Carine; Crozat, Karine; Manglani, Monica; Liu, Zhaoyuan; Ginhoux, Florent; McGavern, Dorian B.; Dalod, Marc; Malissen, Bernard; Lawrence, Toby; Rua, Réjane

doi:10.1016/j.immuni.2022.10.005

Cited by 38 publications

(36 citation statements)

References 62 publications

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“…7, J and K). This implies that type 1 interferon-mediated signaling is critical for the maintenance of MHCII hi macrophage-dependent antiviral barriers at the perisinus, which is in line with the recent report by Rebejac et al (20).…”

Section: The Venous Sinus-associated Macrophage Barrier Protects Agai...supporting

confidence: 90%

“…Nevertheless, there is some controversy about the roles of the dural immune system in the pathogenesis of CNS autoimmune diseases: Not only is CNS antigen–specific T cell trafficking confined to the leptomeninges but CNS antigens are also not very accessible to the dura ( 19 ). Considering the peripheral location of the dura, clarifying the specific responses of the dural immune system to systemic pathogens is important and beginning to be understood ( 20 ). Although adaptive immune cells such as plasma cells at the dural venous sinus protect against fungal infection ( 21 ), an understanding of how innate immune cells respond to peripheral pathogens has been elusive.…”

Section: Introductionmentioning

confidence: 99%

“…Although adaptive immune cells such as plasma cells at the dural venous sinus protect against fungal infection ( 21 ), an understanding of how innate immune cells respond to peripheral pathogens has been elusive. Border-associated macrophages—innate immune cells that function in host defense and maintain tissue homeostasis—include major histocompatibility complex class II (MHCII) hi and MHCII lo macrophages and are extensively distributed in CNS border tissues ( 20 , 22 , 23 ). A recent report ( 24 ) demonstrates that the border-associated macrophages serve as the immune barrier for CNS protection but subsequently facilitate monocyte infiltration across the CNS border tissues when the Trypanosoma brucei parasite invades the border tissues.…”

Section: Introductionmentioning

confidence: 99%

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Immaturity of immune cells around the dural venous sinuses contributes to viral meningoencephalitis in neonates

Kim,

Ahn,

Jin

et al. 2023

Sci. Immunol.

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High neonatal susceptibility to meningitis has been attributed to the anatomical barriers that act to protect the central nervous system (CNS) from infection being immature and not fully developed. However, the mechanisms by which pathogens breach CNS barriers are poorly understood. Using the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) to study virus propagation into the CNS during systemic infection, we demonstrate that mortality in neonatal, but not adult, mice is high after infection. Virus propagated extensively from the perivenous sinus region of the dura mater to the leptomeninges, choroid plexus, and cerebral cortex. Although the structural barrier of CNS border tissues is comparable between neonates and adults, immunofluorescence staining and single-cell RNA sequencing analyses revealed that the neonatal dural immune cells are immature and predominantly composed of CD206 hi macrophages, with major histocompatibility complex class II (MHCII) hi macrophages being rare. In adults, however, perivenous sinus immune cells were enriched in MHCII hi macrophages that are specialized for producing antiviral molecules and chemokines compared with CD206 hi macrophages and protected the CNS against systemic virus invasion. Our findings clarify how systemic pathogens enter the CNS through its border tissues and how the immune barrier at the perivenous sinus region of the dura blocks pathogen access to the CNS.

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Section: The Venous Sinus-associated Macrophage Barrier Protects Agai...supporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immaturity of immune cells around the dural venous sinuses contributes to viral meningoencephalitis in neonates

Kim,

Ahn,

Jin

et al. 2023

Sci. Immunol.

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“…For instance, intracranial injection of lymphocytic choriomeningitis virus (LCMV) resulted in infection and death of resident dural meningeal macrophages and long‐term engraftment of blood‐derived monocytes in the dura mater, which displayed impaired immune functions [9]. Dural BAMs could also react to systemic inflammation, as shown after peripheral injection of lipopolysaccharide, SARS‐CoV‐2, or LCMV [10]. In contrast to the intracranial route of infection, peripheral LCMV infection was asymptomatic in immunocompetent mice, but our results showed that depletion of dural meningeal macrophages led to increased brain viral load and fatal meningitis that recapitulated an intracranial infection [10].…”

Section: Antimicrobial Functions Of the Meningesmentioning

confidence: 99%

“…Dural BAMs could also react to systemic inflammation, as shown after peripheral injection of lipopolysaccharide, SARS-CoV-2, or LCMV [10]. In contrast to the intracranial route of infection, peripheral LCMV infection was asymptomatic in immunocompetent mice, but our results showed that depletion of dural meningeal macrophages led to increased brain viral load and fatal meningitis that recapitulated an intracranial infection [10]. In addition, peripheral infection of mice with Trypanosoma brucei (the agent of sleeping sickness) led to parasite invasion of the brain borders and the parenchyma.…”

Section: Antimicrobial Functions Of Immune Meningeal Cellsmentioning

confidence: 99%

Meningeal regulation of infections: A double‐edged sword

Eme‐Scolan,

Arnaud‐Paroutaud,

Haidar

et al. 2023

Eur J Immunol

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In the past 10 years, important discoveries have been made in the field of neuroimmunology, especially regarding brain borders. Indeed, meninges are protective envelopes surrounding the CNS and are currently in the spotlight, with multiple studies showing their involvement in brain infection and cognitive disorders. In this review, we describe the meningeal layers and their protective role in the CNS against bacterial, viral, fungal, and parasitic infections, by immune and nonimmune cells. Moreover, we discuss the neurological and cognitive consequences resulting from meningeal infections in neonates (e.g. infection with group B Streptococcus, cytomegalovirus, …) or adults (e.g. infection with Trypanosoma brucei, Streptococcus pneumoniae, …). We hope that this review will bring to light an integrated view of meningeal immune regulations during CNS infections and their neurological consequences.

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Key roles of glial cells in the encephalopathy of prematurity

Van Steenwinckel,

Bokobza,

Laforge

et al. 2023

Glia

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Across the globe, approximately one in 10 babies are born preterm, that is, before 37 weeks of a typical 40 weeks of gestation. Up to 50% of preterm born infants develop brain injury, encephalopathy of prematurity (EoP), that substantially increases their risk for developing lifelong defects in motor skills and domains of learning, memory, emotional regulation, and cognition. We are still severely limited in our abilities to prevent or predict preterm birth. No longer just the “support cells,” we now clearly understand that during development glia are key for building a healthy brain. Glial dysfunction is a hallmark of EoP, notably, microgliosis, astrogliosis, and oligodendrocyte injury. Our knowledge of glial biology during development is exponentially expanding but hasn't developed sufficiently for development of effective neuroregenerative therapies. This review summarizes the current state of knowledge for the roles of glia in infants with EoP and its animal models, and a description of known glial‐cell interactions in the context of EoP, such as the roles for border‐associated macrophages. The field of perinatal medicine is relatively small but has worked passionately to improve our understanding of the etiology of EoP coupled with detailed mechanistic studies of pre‐clinical and human cohorts. A primary finding from this review is that expanding our collaborations with computational biologists, working together to understand the complexity of glial subtypes, glial maturation, and the impacts of EoP in the short and long term will be key to the design of therapies that improve outcomes.

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Meningeal macrophages protect against viral neuroinfection

Cited by 38 publications

References 62 publications

Immaturity of immune cells around the dural venous sinuses contributes to viral meningoencephalitis in neonates

Immaturity of immune cells around the dural venous sinuses contributes to viral meningoencephalitis in neonates

Meningeal regulation of infections: A double‐edged sword

Key roles of glial cells in the encephalopathy of prematurity

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