TRIM21 negatively regulates Corynebacterium pseudotuberculosis-induced inflammation and is critical for the survival of C. pseudotuberculosis infected C57BL6 mice

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-1 alpha, IL-1 beta, IL-6, and TNF-alpha 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.

Automated summary

TRIM21 plays a crucial role in preventing C. pseudotuberculosis infection by limiting bacterial replication in macrophages and protecting infected cells from death. The absence of TRIM21 results in higher mortality, bacterial load, abscess formation, and organ lesions in C. pseudotuberculosis-infected mice, along with increased secretion of pro-inflammatory cytokines in macrophages, sera, organs, and ascites.