Nonredundancy of IL-1α and IL-1ß is defined by distinct regulation of tissues orchestrating resistance versus tolerance to infection.
Sci Adv
; 8(9): eabj7293, 2022 03 04.
Article
em En
| MEDLINE
| ID: mdl-35235356
ABSTRACT
Interleukin-1α (IL-1α) and IL-1ß 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-1ß functions that drive protective responses against invasive infection with group A Streptococcus. IL-1ß 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-1ß was critical for the regulation of the spleen transcriptome, which correlated with ample IL-1ß expression in this tissue. The results identify distinct and organ-specific roles of IL-1α versus IL-1ß and implicate spatial restriction of their expression and bioavailability during infection as the underlying mechanism.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-1alfa
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Áustria