Neutrophil-derived IL-1β Is Sufficient for Abscess Formation in Immunity against Staphylococcus aureus in Mice

PLoS Pathogens

Yoichiro Iwakura¹  Jennifer L. Granick²  Scott I. Simon²  Lloyd S. Miller³  Akira Takashima⁴  Hironori Matsushima⁴  Yi Guo⁵  Frank Hebroni⁵  Romela Irene Ramos⁵  John S. Cho⁵  Ambrose L. Cheung⁶  Genhong Cheng⁷  Delphine J. Lee⁸  Caiyun Xuan⁸  Seema B. Plaisier⁸ 

[1] Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Saitama, Japan;Department of Biomedical Engineering, University of California Davis, Davis, California, United States of America;Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America;Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, Ohio, United States of America;Department of Medicine, Division of Dermatology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California, United States of America;Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire, United States of America;Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California, United States of America;Department of Translational Immunology, Dirks/Dougherty Laboratory for Cancer Research, John Wayne Cancer Institute, Santa Monica, California, United States of America

关键词: Neutrophils;    Staphylococcus aureus;    Skin infections;    Mouse models;    Abscesses;    Monocytes;    Methicillin-resistant Staphylococcus aureus;    Inflammasomes;   

DOI  :  10.1371/journal.ppat.1003047

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Neutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis and in vivo multispectral noninvasive imaging during the S. aureus infection revealed a strong functional and temporal association between neutrophil recruitment and IL-1β/IL-1R activation. Unexpectedly, neutrophils but not monocytes/macrophages or other MHCII-expressing antigen presenting cells were the predominant source of IL-1β at the site of infection. Furthermore, neutrophil-derived IL-1β was essential for host defense since adoptive transfer of IL-1β-expressing neutrophils was sufficient to restore the impaired neutrophil abscess formation in S. aureus-infected IL-1β-deficient mice. S. aureus-induced IL-1β production by neutrophils required TLR2, NOD2, FPR1 and the ASC/NLRP3 inflammasome in an α-toxin-dependent mechanism. Taken together, IL-1β and neutrophil abscess formation during an infection are functionally, temporally and spatially linked as a consequence of direct IL-1β production by neutrophils.

【 授权许可】

CC BY