TRAF1 suppresses antifungal immunity through CXCL1-mediated neutrophil recruitment during Candida albicans intradermal infection

• DOI: 10.1186/s12964-020-00532-x
• Publication Date: 2020-02-24T08:05:47Z
• Authors: Wenjuan Bai; Qingqing Wang; Zihou Deng; Tiantian Li; Hui Xiao; Zhiyuan Wu
• Keywords: Proinflammatory cytokine; CXCL1; CXCL2

Abstract Background Candida albicans is the most common opportunistic human fungal pathogen. The chemokine ligand CXCL1 plays a protective role in infection through recruitment of neutrophils. TRAF1 (tumor necrosis factor-associated factor 1) can be highly induced by proinflammatory stimuli such as LPS and TNF has been implicated septic shock. However, infection, especially remains elusive. Herein, we reveal that suppresses antifungal immune response to intradermal regulation induction neutrophil recruitment. Methods A mouse model C. was established. Traf1 −/− mice immortalized keratinocytes were generated. p65 inhibitor triptolide, STAT1 fludarabine, neutrophil-depletion antibody Ly6G, neutralizing for utilized. expression cytokines chemokines assessed real-time PCR ELISA, activation signaling molecules analyzed Western blotting. Hematoxylin eosin staining periodic acid Schiff used histology or detection, respectively. immunofluorescence flow cytometry analyses employed assessment cell infiltration. Bone marrow transplantation adoptive transfer experiments conducted establish macrophage compartment skin infection. Results TRAF1-deficient demonstrated improved control concomitant increase reduction burden. upregulated macrophages treated with heat-killed . Mechanistically, showed increased transcription NFκB p65. CXCL8 also upon stimulation decreasing STAT1. played critical containing vivo. Conclusion better skin, process attributable CXCL-neutrophil axis. likely regulates both transcriptional STAT1, Our finding offers new insight into understanding regulatory mechanisms host defense against Graphical abstract