| First Author | Batista SJ | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 3687 |
| PubMed ID | 32703941 | Mgi Jnum | J:293007 |
| Mgi Id | MGI:6447333 | Doi | 10.1038/s41467-020-17491-z |
| Citation | Batista SJ, et al. (2020) Gasdermin-D-dependent IL-1alpha release from microglia promotes protective immunity during chronic Toxoplasma gondii infection. Nat Commun 11(1):3687 |
| abstractText | Microglia, resident immune cells of the CNS, are thought to defend against infections. Toxoplasma gondii is an opportunistic infection that can cause severe neurological disease. Here we report that during T. gondii infection a strong NF-kappaB and inflammatory cytokine transcriptional signature is overrepresented in blood-derived macrophages versus microglia. Interestingly, IL-1alpha is enriched in microglia and IL-1beta in macrophages. We find that mice lacking IL-1R1 or IL-1alpha, but not IL-1beta, have impaired parasite control and immune cell infiltration within the brain. Further, we show that microglia, not peripheral myeloid cells, release IL-1alpha ex vivo. Finally, we show that ex vivo IL-1alpha release is gasdermin-D dependent, and that gasdermin-D and caspase-1/11 deficient mice show deficits in brain inflammation and parasite control. These results demonstrate that microglia and macrophages are differently equipped to propagate inflammation, and that in chronic T. gondii infection, microglia can release the alarmin IL-1alpha, promoting neuroinflammation and parasite control. |
