title: Neutrophil-derived IL-1β is sufficient for abscess formation in immunity against Staphylococcus aureus in mice.
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.
authors.affiliation: Department of Medicine, Division of Dermatology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: John S
authors.initials: JS
authors.lastname: Cho
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Romela Irene
authors.initials: RI
authors.lastname: Ramos
authors.forename: Frank
authors.initials: F
authors.lastname: Hebroni
authors.forename: Seema B
authors.initials: SB
authors.lastname: Plaisier
authors.forename: Caiyun
authors.initials: C
authors.lastname: Xuan
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Granick
authors.forename: Hironori
authors.initials: H
authors.lastname: Matsushima
authors.forename: Akira
authors.initials: A
authors.lastname: Takashima
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Ambrose L
authors.initials: AL
authors.lastname: Cheung
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.forename: Delphine J
authors.initials: DJ
authors.lastname: Lee
authors.forename: Scott I
authors.initials: SI
authors.lastname: Simon
authors.forename: Lloyd S
authors.initials: LS
authors.lastname: Miller
mesh_terms: D000038:Abscess / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D019264:Adoptive Transfer; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013207:Staphylococcal Skin Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C469988:Fpr1 protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D044042:Receptors, Formyl Peptide; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2