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

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-1 beta/IL-1R activation. Unexpectedly, neutrophils but not monocytes/macrophages or other MHCII-expressing antigen presenting cells were the predominant source of IL-1 beta at the site of infection. Furthermore, neutrophil-derived IL-1 beta was essential for host defense since adoptive transfer of IL-1 beta-expressing neutrophils was sufficient to restore the impaired neutrophil abscess formation in S. aureus-infected IL-1 beta-deficient mice. S. aureus-induced IL-1 beta production by neutrophils required TLR2, NOD2, FPR1 and the ASC/NLRP3 inflammasome in an alpha-toxin-dependent mechanism. Taken together, IL-1 beta and neutrophil abscess formation during an infection are functionally, temporally and spatially linked as a consequence of direct IL-1 beta production by neutrophils.