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.

MyD88 in Macrophages Is Critical for Abscess Resolution in Staphylococcal Skin Infection

“…PMLs exit the bone marrow in response to inflammatory stimuli and contribute to the fast clearance of bacteria via an elaborate antimicrobial machinery (40,41). PML-derived IL-1b contributes to abscess formation in S. aureus infection (21). However, we show in this article that, when dermal Mfs fail to immediately recruit PMLs to the site of staphylococcal invasion, the finally arriving and fully activated PMLs fail to timely control the infection.…”

The psm α Locus Regulates Production of Staphylococcus aureus Alpha-Toxin during Infection

“…Similarly, Hla elicits chemokine and cytokine release from host immune cells, epithelial cells, and endothelial cells (59)(60)(61)(62)(63)(64)(65), including the proinflammatory cytokine interleukin-1␤ (IL-1␤), an indicator of inflammasome activation and a major cytokine involved in the recruitment of neutrophils to the site of infection (66). Primary neutrophils display resistance to the lytic effects of Hla unless this toxin is present at high concentrations that would not likely be achieved early in the course of infection (65,67).…”

Clonally expanded γδ T cells protect against Staphylococcus aureus skin reinfection

“…Therefore, we evaluated the 1° and 2° S. aureus skin infections in IL-1β -/-mice, which have impaired neutrophil recruitment and host defense during a 1° S. aureus skin infection (13). The 1° IL-1β -/-mice developed markedly larger lesions and increased bacterial burden compared with WT mice (Figure 1, B-F).…”