| First Author | Norris GT | Year | 2023 |
| Journal | PLoS Pathog | Volume | 19 |
| Issue | 11 | Pages | e1011350 |
| PubMed ID | 37983247 | Mgi Jnum | J:343483 |
| Mgi Id | MGI:7564884 | Doi | 10.1371/journal.ppat.1011350 |
| Citation | Norris GT, et al. (2023) Oligodendrocyte-derived IL-33 functions as a microglial survival factor during neuroinvasive flavivirus infection. PLoS Pathog 19(11):e1011350 |
| abstractText | 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. |
