| First Author | Eislmayr K | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 9 | Pages | eabj7293 |
| PubMed ID | 35235356 | Mgi Jnum | J:334669 |
| Mgi Id | MGI:7256047 | Doi | 10.1126/sciadv.abj7293 |
| Citation | Eislmayr K, et al. (2022) Nonredundancy of IL-1alpha and IL-1beta is defined by distinct regulation of tissues orchestrating resistance versus tolerance to infection. Sci Adv 8(9):eabj7293 |
| abstractText | Interleukin-1alpha (IL-1alpha) and IL-1beta are inflammatory cytokines with important roles in health and disease. They trigger the same receptor and elicit comparable cellular responses but, for poorly understood reasons, are not redundant in vivo. Here, we decoupled IL-1alpha and IL-1beta functions that drive protective responses against invasive infection with group A Streptococcus. IL-1beta was essential for pathogen clearance, hence resistance to infection, by inducing granulocyte colony-stimulating factor at the infection site and establishing emergency granulopoiesis. In contrast, IL-1alpha governed reprogramming of liver metabolic pathways associated with tolerance to infection. The IL-1alpha-dominated hepatic regulation corresponded to high IL-1alpha levels in the liver during infection. Conversely, IL-1beta was critical for the regulation of the spleen transcriptome, which correlated with ample IL-1beta expression in this tissue. The results identify distinct and organ-specific roles of IL-1alpha versus IL-1beta and implicate spatial restriction of their expression and bioavailability during infection as the underlying mechanism. |
