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TRIM32 reduced the recruitment of innate immune cells and the killing capacity of Listeria monocytogenes by inhibiting secretion of chemokines

Listeria monocytogenes (Lm) is a facultative, intracellular Gram-positive pathogenic bacterium that causes sepsis, a condition characterized by persistent excessive inflammation and organ dysfunction. However, the pathogenesis of Lm-induced sepsis is unknown. In this research, we discovered that TRI...

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Detalles Bibliográficos
Autores principales: OuYang, Xuan, Liu, Peng, Zheng, Yuling, Jiang, Hua, Lv, Qingyu, Huang, Wenhua, Hao, Huaijie, Pian, Yaya, Kong, Decong, Jiang, Yongqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324126/
https://www.ncbi.nlm.nih.gov/pubmed/37415157
http://dx.doi.org/10.1186/s13099-023-00558-9
Descripción
Sumario:Listeria monocytogenes (Lm) is a facultative, intracellular Gram-positive pathogenic bacterium that causes sepsis, a condition characterized by persistent excessive inflammation and organ dysfunction. However, the pathogenesis of Lm-induced sepsis is unknown. In this research, we discovered that TRIM32 is required for innate immune regulation during Lm infection. Trim32 deficiency remarkably reduced bacteremia and proinflammatory cytokine secretion in mice with severe Lm infection, preventing sepsis. Trim32(−/−) mice had a lower bacterial burden after Lm infection and survived significantly longer than wild-type (WT) mice, as well as lower serum levels of inflammatory cytokines TNF-α, IL-6, IL-18, IL-12p70, IFN-β, and IFN-γ at 1 day post infection (dpi) compared to WT mice. On the other hand, the chemokines CXCL1, CCL2, CCL7, and CCL5 were enhanced at 3 dpi in Trim32(−/−) mice than WT mice, reflecting increased recruitment of neutrophils and macrophages. Furthermore, Trim32(−/−) mice had higher levels of macrophage-associated iNOS to kill Lm. Collectively, our findings suggest that TRIM32 reduces innate immune cells recruitment and Lm killing capabilities via iNOS production. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13099-023-00558-9.