Salmonella manipulates macrophage migration via SteC-mediated myosin light chain activation to penetrate the gut-vascular barrier.

The intestinal pathogen Salmonella enterica rapidly enters the bloodstream after the invasion of intestinal epithelial cells, but how Salmonella breaks through the gut-vascular barrier is largely unknown. Here, we report that Salmonella enters the bloodstream through intestinal CX3CR1+ macrophages during early infection. Mechanistically, Salmonella induces the migration/invasion properties of macrophages in a manner dependent on host cell actin and on the pathogen effector SteC. SteC recruits host myosin light chain protein Myl12a and phosphorylates its Ser19 and Thr20 residues. Myl12a phosphorylation results in actin rearrangement, and enhanced migration and invasion of macrophages. SteC is able to utilize a wide range of NTPs other than ATP to phosphorylate Myl12a. We further solved the crystal structure of SteC, which suggests an atypical dimerization-mediated catalytic mechanism. Finally, in vivo data show that SteC-mediated cytoskeleton manipulation is crucial for Salmonella breaching the gut vascular barrier and spreading to target organs.

Prognostic significance of soluble CD25 in patients with sepsis: a prospective observational study.

OBJECTIVES: The diagnosis of sepsis is challenging, the need for sensitive and specific diagnostic and prognostic biomarkers has not been met. Soluble CD25 (sCD25) is a readily available biomarker reported to represent the severity of the disease. This study aimed to assess the association between sCD25 and mortality in patients with sepsis. METHODS: In total, 329 adult patients with sepsis were screened through a prospective, observational study. We investigated the severity scores and sCD25 levels at admission to the intensive care unit (ICU), defined by sepsis (sepsis-3). The prognostic value of sCD25 was assessed using receiver operating characteristic (ROC) curves and binary logistic regression models in predicting unfavourable outcome. The correlations between variables and severity of disease were analysed by Spearman correlation tests. RESULTS: After entering the ICU, the sCD25 level and sequential organ failure assessment (SOFA) score were significantly higher in nonsurvivors than in survivors. The prognostic values estimated by the ROC curves were 0.678 for sCD25 and 0.945 for SOFA score at ICU admission. sCD25 had a modest ability to predict poor outcome. Logistic regression showed that increased levels of sCD25 were independently associated with unfavourable outcome. Spearman correlation tests showed that sCD25 levels were positively correlated with disease severity. CONCLUSIONS: In sepsis patients, increased sCD25 levels were independently associated with poor clinical outcomes. Further research is needed to improve the understanding of the pathophysiology of this relationship.