IL-1R activation is required for neutrophil recruitment in an effective innate immune response against Staphylococcus aureus infection. In this study, we investigated the mechanism of IL-1R activation in vivo in a model of S. aureus infection. In response to a S. aureus cutaneous challenge, mice deficient in IL-1β, IL-1α/IL-1β, but not IL-1α, developed larger lesions with higher bacterial counts and had decreased neutrophil recruitment compared with wild-type mice. Neutrophil recruitment and bacterial clearance required IL-1β expression by bone marrow (BM)-derived cells and not by non-BM-derived resident cells. In addition, mice deficient in the inflammasome component apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) had the same defects in neutrophil recruitment and host defense as IL-1β-deficient mice, demonstrating an essential role for the inflammasome in mediating the production of active IL-1β to promote neutrophil recruitment in host defense against S. aureus. This finding was further supported by the ability of recombinant active IL-1β to control the infection and promote bacterial clearance in IL-1β-deficient mice. These studies define a key host defense circuit where inflammasome-mediated IL-1β production by BM-derived cells signals IL-1R on non-BM-derived resident cells to activate neutrophil recruitment in the innate immune response against S. aureus in vivo.
|Original language||English (US)|
|Number of pages||10|
|Journal||Journal of Immunology|
|State||Published - Nov 15 2007|
ASJC Scopus subject areas
- Immunology and Allergy