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. 2007 Nov 15;179(10):6933-42.
doi: 10.4049/jimmunol.179.10.6933.

Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo

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Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo

Lloyd S Miller et al. J Immunol. .

Erratum in

  • J Immunol. 2008 Jan 1;180(1):665

Abstract

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.

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