| First Author | Miller LS | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 10 | Pages | 6933-42 |
| PubMed ID | 17982084 | Mgi Jnum | J:153859 |
| Mgi Id | MGI:4366416 | Doi | 10.4049/jimmunol.179.10.6933 |
| Citation | Miller LS, et al. (2007) Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo. J Immunol 179(10):6933-42 |
| abstractText | 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-1beta, IL-1alpha/IL-1beta, but not IL-1alpha, developed larger lesions with higher bacterial counts and had decreased neutrophil recruitment compared with wild-type mice. Neutrophil recruitment and bacterial clearance required IL-1beta 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-1beta-deficient mice, demonstrating an essential role for the inflammasome in mediating the production of active IL-1beta to promote neutrophil recruitment in host defense against S. aureus. This finding was further supported by the ability of recombinant active IL-1beta to control the infection and promote bacterial clearance in IL-1beta-deficient mice. These studies define a key host defense circuit where inflammasome-mediated IL-1beta 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. |
