Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Abscess / genetics
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Abscess / immunology*
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Abscess / metabolism
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Abscess / microbiology
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Abscess / pathology
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Adoptive Transfer
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Carrier Proteins / metabolism
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Inflammasomes / genetics
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Inflammasomes / immunology
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Inflammasomes / metabolism
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Interleukin-1beta / biosynthesis
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Interleukin-1beta / genetics
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Interleukin-1beta / immunology*
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Mice
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Mice, Mutant Strains
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NLR Family, Pyrin Domain-Containing 3 Protein
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Neutrophils / immunology*
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Neutrophils / metabolism
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Neutrophils / pathology
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Nod2 Signaling Adaptor Protein / genetics
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Nod2 Signaling Adaptor Protein / immunology
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Nod2 Signaling Adaptor Protein / metabolism
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Receptors, Formyl Peptide / genetics
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Receptors, Formyl Peptide / immunology
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Receptors, Formyl Peptide / metabolism
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Staphylococcal Skin Infections / genetics
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Staphylococcal Skin Infections / immunology*
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Staphylococcal Skin Infections / metabolism
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Staphylococcal Skin Infections / microbiology
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Staphylococcal Skin Infections / pathology
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Staphylococcus aureus / immunology*
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Toll-Like Receptor 2 / genetics
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Toll-Like Receptor 2 / immunology
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Toll-Like Receptor 2 / metabolism
Substances
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Carrier Proteins
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Fpr1 protein, mouse
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Inflammasomes
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Interleukin-1beta
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nlrp3 protein, mouse
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Nod2 Signaling Adaptor Protein
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Nod2 protein, mouse
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Receptors, Formyl Peptide
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Tlr2 protein, mouse
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Toll-Like Receptor 2