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Inflammation Research
Erschienen in: Inflammation Research 1/2024

23.12.2023 | Original Research Paper

Salmonella spvC gene suppresses macrophage/neutrophil antibacterial defense mediated by gasdermin D

verfasst von: Liting Zhou, Yuanyuan Li, Jiayi You, Chaoyi Wu, Lingli Zuo, Yilin Chen, Li Kang, Zhengyu Zhou, Rui Huang, Shuyan Wu

Erschienen in: Inflammation Research | Ausgabe 1/2024

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Abstract

Objective

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a representative model organism for investigating host–pathogen interactions. It was reported that S. Typhimurium spvC gene alleviated intestinal inflammation to aggravate systemic infection, while the precise mechanisms remain unclear. In this study, the influence of spvC on the antibacterial defense of macrophage/neutrophil mediated by gasdermin D (GSDMD) was investigated.

Methods

Mouse macrophage-like cell lines J774A.1 and RAW264.7, neutrophil-like cells derived from HL-60 cells (human promyletic leukemia cell lines) were infected with S. Typhimurium wild type, spvC deletion and complemented strains. Cell death was evaluated by LDH release and Annexin V-FITC/PI staining. Macrophage pyroptosis and neutrophil NETosis were detected by western blotting, live cell imaging and ELISA. Flow cytometry was used to assess the impact of spvC on macrophage-neutrophil cooperation in macrophage (dTHP-1)-neutrophil (dHL-60) co-culture model pretreated with GSDMD inhibitor disulfiram. Wild-type and Gsdmd−/− C57BL/6J mice were utilized for in vivo assay. The degree of phagocytes infiltration and inflammation were analyzed by immunofluorescence and transmission electron microscopy.

Results

Here we find that spvC inhibits pyroptosis in macrophages via Caspase-1/Caspase-11 dependent canonical and non-canonical pathways, and restrains neutrophil extracellular traps extrusion in GSDMD-dependent manner. Moreover, spvC could ameliorate macrophages/neutrophils infiltration and cooperation in the inflammatory response mediated by GSDMD to combat Salmonella infection.

Conclusions

Our findings highlight the antibacterial activity of GSDMD in phagocytes and reveal a novel pathogenic mechanism employed by spvC to counteract this host defense, which may shed new light on designing effective therapeutics to control S. Typhimurium infection.
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Metadaten
Titel
Salmonella spvC gene suppresses macrophage/neutrophil antibacterial defense mediated by gasdermin D
verfasst von
Liting Zhou
Yuanyuan Li
Jiayi You
Chaoyi Wu
Lingli Zuo
Yilin Chen
Li Kang
Zhengyu Zhou
Rui Huang
Shuyan Wu
Publikationsdatum
23.12.2023
Verlag
Springer International Publishing
Erschienen in
Inflammation Research / Ausgabe 1/2024
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-023-01818-9

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