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

Lloyd S. Miller, Eric M. Pietras, Lawrence H. Uricchio, Kathleen Hirano, Shyam Rao, Heping Lin, Ryan M. O'Connell, Yoichiro Iwakura, Ambrose L. Cheung, Genhong Cheng, Robert L. Modlin

Research output: Contribution to journalArticle

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-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 languageEnglish (US)
Pages (from-to)6933-6942
Number of pages10
JournalJournal of Immunology
Volume179
Issue number10
StatePublished - Nov 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Miller, L. S., Pietras, E. M., Uricchio, L. H., Hirano, K., Rao, S., Lin, H., O'Connell, R. M., Iwakura, Y., Cheung, A. L., Cheng, G., & Modlin, R. L. (2007). Inflammasome-mediated production of IL-1β is required for neutrophil recruitment against Staphylococcus aureus in vivo. Journal of Immunology, 179(10), 6933-6942.