title: Protective role of IL-1β against post-arthroplasty Staphylococcus aureus infection.
abstract: MyD88 is an adapter molecule that is used by both IL-1R and TLR family members to initiate downstream signaling and promote immune responses. Given that IL-1β is induced after Staphylococcus aureus infections and TLR2 is activated by S. aureus lipopeptides, we hypothesized that IL-1β and TLR2 contribute to MyD88-dependent protective immune responses against post-arthroplasty S. aureus infections. To test this hypothesis, we used a mouse model of a post-arthroplasty S. aureus infection to compare the bacterial burden, biofilm formation and neutrophil recruitment in IL-1β-deficient, TLR2-deficient and wild-type (wt) mice. By using in vivo bioluminescence imaging, we found that the bacterial burden in IL-1β-deficient mice was 26-fold higher at 1 day after infection and remained 3- to 10-fold greater than wt mice through day 42. In contrast, the bacterial burden in TLR2-deficient mice did not differ from wt mice. In addition, implants harvested from IL-1β-deficient mice had more biofilm formation and 14-fold higher adherent bacteria compared with those from wt mice. Finally, IL-1β-deficient mice had ∼50% decreased neutrophil recruitment to the infected postoperative joints than wt mice. Taken together, these findings suggest a mechanism by which IL-1β induces neutrophil recruitment to help control the bacterial burden and the ensuing biofilm formation in a post-surgical joint.
authors: Orthopaedic Hospital Research Center, Orthopaedic Hospital Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California, Los Angeles, California, USA.
authors: Nicholas M
authors: NM
authors: Bernthal
authors: Jonathan R
authors: JR
authors: Pribaz
authors: Alexandra I
authors: AI
authors: Stavrakis
authors: Fabrizio
authors: F
authors: Billi
authors: John S
authors: JS
authors: Cho
authors: Romela Irene
authors: RI
authors: Ramos
authors: Kevin P
authors: KP
authors: Francis
authors: Yoichiro
authors: Y
authors: Iwakura
authors: Lloyd S
authors: LS
authors: Miller
mesh_terms: D000818:Animals; D001178:Arthroplasty; D018441:Biofilms / Q000254:growth & development; D001864:Bone Wires / Q000382:microbiology; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D020556:Neutrophil Infiltration; D016459:Prosthesis-Related Infections / Q000276:immunology* / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology* / Q000378:metabolism; D013211:Staphylococcus aureus; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2