TRIM32 reduced the recruitment of innate immune cells and the killing capacity of Listeria monocytogenes by inhibiting secretion of chemokines.
TRIM32 reduced the recruitment of innate immune cells and the killing capacity of Listeria monocytogenes by inhibiting secretion of chemokines.
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DOI：
10.1186/s13099-023-00558-9
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发表时间：
2023-07-06
期刊：
影响因子：
4.2
通讯作者：
中科院分区：
文献类型：
--
作者：
单核增生李斯特菌（Lm）是一种兼性的细胞内革兰氏阳性致病菌，可引起脓毒症，其特征是持续过度炎症和器官功能障碍。然而，lm致脓毒症的发病机制尚不清楚。在本研究中，我们发现TRIM32是Lm感染过程中先天免疫调节所必需的。Trim32缺乏显著减少严重Lm感染小鼠的菌血症和促炎细胞因子分泌，预防败血症。Trim32−/−小鼠感染Lm后细菌负荷较低，存活时间明显长于野生型（WT）小鼠，感染后1天血清炎症因子TNF-α、IL-6、IL-18、IL-12p70、IFN-β和IFN-γ水平也低于野生型小鼠（dpi）。另一方面，在Trim32−/−小鼠中，趋化因子CXCL1、CCL2、CCL7和CCL5在3 dpi时比WT小鼠增强，反映了中性粒细胞和巨噬细胞的募集增加。此外，Trim32−/−小鼠具有更高水平的巨噬细胞相关iNOS来杀死Lm。总的来说，我们的研究结果表明TRIM32通过iNOS的产生降低了先天免疫细胞的募集和Lm杀伤能力。在线版本包含补充材料，可在10.1186/s13099-023-00558-9获得。
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. The online version contains supplementary material available at 10.1186/s13099-023-00558-9.
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