Nonredundancy of IL-1α and IL-1β is defined by distinct regulation of tissues orchestrating resistance versus tolerance to infection.

ABSTRACT: Interleukin-1α (IL-1α) and IL-1β 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-1α and IL-1β functions that drive protective responses against invasive infection with group A Streptococcus. IL-1β 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-1α governed reprogramming of liver metabolic pathways associated with tolerance to infection. The IL-1α-dominated hepatic regulation corresponded to high IL-1α levels in the liver during infection. Conversely, IL-1β

SUBMITTER: Eislmayr K 

PROVIDER: S-EPMC8890706 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature