Corynebacterium pseudotuberculosis, a facultative intracellular bacterium, is an important zoonotic pathogen responsible for chronic inflammatory diseases. TRIM21, an E3 ubiquitin-protein ligase, plays pivotal roles in inflammation regulation. However, its role during C. pseudotuberculosis infection is unclear. Here, we found that TRIM21 expression was significantly increased in C. pseudotuberculosis-infected macrophages. Following infection by C. pseudotuberculosis, we observed a significantly higher number of bacteria and a higher degree of LDH release from Trim21^-/- macrophages compared to wild-type (WT) macrophages, suggesting that TRIM21 limits C. pseudotuberculosis replication in macrophages and protects the infected cells from death. Further in vivo experiments showed a significantly higher mortality, higher bacterial load, much more severe abscess formation, and lesions in the organs of C. pseudotuberculosis-infected Trim21^-/- mice compared to those of the infected WT mice, suggesting that TRIM21 plays critical roles in protecting against C. pseudotuberculosis infection. Moreover, the secretory levels of IL-1α, IL-1β, IL-6, and TNF-α were significantly higher in C. pseudotuberculosis-infected Trim21^-/- macrophages compared to infected WT macrophages; the levels of these cytokines were also higher in the sera, organs, and ascites of C. pseudotuberculosis-infected Trim21^-/- mice compared to infected WT mice. These findings suggest that TRIM21 negatively regulates the secretion of pro-inflammatory cytokines in macrophages, sera, organs, and ascites of mice following C. pseudotuberculosis infection. Collectively, the present study demonstrates that TRIM21 plays a vital role in preventing C. pseudotuberculosis infection, which may be related to the negative regulation of pro-inflammatory cytokines production by TRIM21 during this pathogen infection.

假结核棒状杆菌是一种兼性细胞内细菌，是一种重要的人畜共患病病原体，可导致慢性炎症疾病。TRIM21 是一种 E3 泛素蛋白连接酶，在炎症调节中起关键作用。然而，其在假结核杆菌感染过程中的作用尚不清楚。在这里，我们发现 TRIM21 表达在假结核梭菌感染的巨噬细胞中显着增加。在被假结核杆菌感染后，我们观察到与野生型 (WT) 巨噬细胞相比，Trim21 ^-/-巨噬细胞的细菌数量显着增加，LDH 释放程度更高，这表明 TRIM21 限制了假结核杆菌在巨噬细胞中复制并保护受感染的细胞免于死亡。进一步的体内实验表明，与感染的 WT 小鼠相比，感染假结核杆菌的 Trim21 ^-/-小鼠的死亡率显着更高，细菌负荷更高，脓肿形成更严重，器官损伤也表明 TRIM21 发挥了关键作用在防止假结核杆菌感染中的作用。此外，IL-1α，IL-1β，IL-6和TNF-α的分泌水平在显著更高C.假感染的TRIM21 ^{- / -}巨噬细胞与感染的 WT 巨噬细胞相比；这些细胞因子的水平也分别在血清中，器官较高，腹水C.假感染的TRIM21 ^{- / -}小鼠相比，被感染的野生型小鼠。这些结果表明，TRIM21促炎性细胞因子的巨噬细胞，血清，器官，并按照小鼠腹水的分泌负调控C.假感染。总的来说，本研究表明 TRIM21 在预防假结核杆菌感染中起着至关重要的作用，这可能与 TRIM21 在这种病原体感染期间对促炎细胞因子产生的负调节有关。