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Oligodendrocyte-derived IL-33 functions as a microglial survival factor during neuroinvasive flavivirus infection

ABSTRACT: Oligodendrocyte-derived IL-33 functions as a microglial survival factor during neuroinvasive flavivirus infection

PROVIDER: PRJNA1010117 | ENA |

REPOSITORIES: ENA

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Oligodendrocyte-derived IL-33 functions as a microglial survival factor during neuroinvasive flavivirus infection

Project description:In order to recover from infection, organisms must balance robust immune responses to pathogens with the tolerance of immune-mediated pathology. This balance is particularly critical within the central nervous system, whose complex architecture, essential function, and limited capacity for self-renewal render it susceptible to both pathogen- and immune-mediated pathology. Here, we identify the alarmin IL-33 and its receptor ST2 as critical for host survival to neuroinvasive flavivirus infection. We identify oligodendrocytes as the critical source of IL-33, and microglia as the key cellular responders. Notably, we find that the IL-33/ST2 axis does not impact viral control or adaptive immune responses; rather, it is required to promote the activation and survival of microglia. In the absence of intact IL-33/ST2 signaling in the brain, neuroinvasive flavivirus infection triggered aberrant recruitment of monocyte-derived peripheral immune cells, increased neuronal stress, and neuronal cell death, effects that compromised organismal survival. These findings identify IL-33 as a critical mediator of CNS tolerance to pathogen-initiated immunity and inflammation.

2023-11-08 | GSE241804 | GEO

Oligodendrocyte-derived IL-33 functions as a microglial survival factor during neuroinvasive flavivirus infection.

| S-EPMC10695366 | biostudies-literature

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice (ATACseq)

Project description:To determine the direct effect of IL-33 on microglial gene expression, we have bulk ATAC-sequenced cortical microglia 4 hours after IL-33 or vehicle i.c.v. injection.

2022-12-12 | GSE218424 | GEO

Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development II

Project description:Neuronal synapse formation and remodeling is essential to central nervous system (CNS) development and is dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this impacts CNS synapses is largely unknown. Here we show that the IL-1 family cytokine Interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.

2018-02-05 | GSE109353 | GEO

Astrocyte-derived Interleukin-33 promotes microglial synapse engulfment and neural circuit development I

2018-02-05 | GSE109352 | GEO

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice (scRNAseq)

Project description:To determine the effect of IL-33 on microglial gene expression, we have scRNA-sequenced cortical microglia from ST2KO and WT mice 4 hours after IL-33 or vehicle i.c.v. injection.

2022-12-12 | GSE218427 | GEO

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice (H3K27ac ChIP-seq)

Project description:To determine the direct effect of IL-33 on microglial gene expression, we have H3K27ac ChIP-sequenced cortical microglia 4 hours after IL-33 or vehicle i.c.v. injection.

2022-12-12 | GSE218426 | GEO

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice (FOS ChIP-seq)

Project description:To determine whether FOS is involved in the IL-33 microglial gene expression response, we have FOS ChIP-sequenced cortical microglia 4 hours after IL-33 i.c.v. injection.

2022-12-12 | GSE218425 | GEO

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice (bulk RNA-seq)

Project description:To determine the direct effect of IL-33 on microglial gene expression, we have bulk RNA-sequenced cortical microglia 4 hours after IL-33 or vehicle i.c.v. injection.

2022-12-12 | GSE218369 | GEO

Deletion of Slc9a1 in Cx3cr1+ cells stimulated microglial subcluster CREB1-BDNF signaling and oligodendrocyte crosstalk

Project description:Microglial Na/H exchanger-1 (NHE1) protein, encoded by Slc9a1, plays a role in white matter demyelination of ischemic stroke brains. In this study, we conducted single cell RNA-seq transcriptome analysis of corpus collosum and external capsule from wild-type (WT) and conditional Slc9a1 knockout (cKO) mice at 3 days post-stroke to study microglia-oligodendrocyte interactions.

2023-11-06 | GSE247102 | GEO

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