Oligodendrocyte-derived IL-33 functions as a microglial survival factor during neuroinvasive flavivirus infection.
PLoS Pathog
; 19(11): e1011350, 2023 Nov.
Article
en En
| MEDLINE
| ID: mdl-37983247
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Microglía
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Infecciones por Flavivirus
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Interleucina-33
Límite:
Animals
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Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article