CXCL12+ dermal fibroblasts play a critical role in neutrophil recruitment and host defense during S. aureus infection. These fibroblasts, primarily located in the reticular dermis, express adipocyte lineage markers and detect IL-17 and TNFα. They promote neutrophil recruitment through the release of CXCR2 ligands and CXCL12, which is regulated by NFKBIZ. Targeted deletion of Il17ra in fibroblasts reduced neutrophil recruitment and increased S. aureus infection. Similar findings were observed in human psoriatic skin, where CXCL12+ fibroblasts abundantly express neutrophil chemotactic factors, which are decreased upon IL-17 targeting. These results show that CXCL12+ dermal fibroblasts are essential for cutaneous neutrophil recruitment and host defense. The study used single-cell RNA sequencing and network analysis to identify the role of these fibroblasts in skin inflammation. The findings suggest that CXCL12+ fibroblasts, which recognize IL-17, are key mediators of neutrophil communication during infection. The study also highlights the importance of IL-17 signaling in activating these fibroblasts and their role in both infectious and non-infectious skin inflammation. The results demonstrate that dermal fibroblasts, particularly CXCL12+ subsets, are essential for host defense against S. aureus and other pathogens. The study provides new insights into the complex interactions between fibroblasts and neutrophils in skin inflammation and host defense.CXCL12+ dermal fibroblasts play a critical role in neutrophil recruitment and host defense during S. aureus infection. These fibroblasts, primarily located in the reticular dermis, express adipocyte lineage markers and detect IL-17 and TNFα. They promote neutrophil recruitment through the release of CXCR2 ligands and CXCL12, which is regulated by NFKBIZ. Targeted deletion of Il17ra in fibroblasts reduced neutrophil recruitment and increased S. aureus infection. Similar findings were observed in human psoriatic skin, where CXCL12+ fibroblasts abundantly express neutrophil chemotactic factors, which are decreased upon IL-17 targeting. These results show that CXCL12+ dermal fibroblasts are essential for cutaneous neutrophil recruitment and host defense. The study used single-cell RNA sequencing and network analysis to identify the role of these fibroblasts in skin inflammation. The findings suggest that CXCL12+ fibroblasts, which recognize IL-17, are key mediators of neutrophil communication during infection. The study also highlights the importance of IL-17 signaling in activating these fibroblasts and their role in both infectious and non-infectious skin inflammation. The results demonstrate that dermal fibroblasts, particularly CXCL12+ subsets, are essential for host defense against S. aureus and other pathogens. The study provides new insights into the complex interactions between fibroblasts and neutrophils in skin inflammation and host defense.