We proposed the hypothesis that high-risk clones of colistin-resistant K. pneumoniae (ColR-Kp) possesses a high number of virulence factors and has enhanced survival capacity against the neutrophil activity. We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive ColR-Kp infections. The ST101 and ST395 ColR-Kp infections had higher 30-day mortality (58%, p = 0.005 and 75%, p = 0.003). The presence of yersiniabactin biosynthesis gene (ybtS) and ferric uptake operon associated gene (kfu) were significantly higher in ST101 (99%, p ≤ 0.001) and ST395 (94%, p < 0.012). Being in ICU (OR: 7.9; CI: 1.43–55.98; p = 0.024), kfu (OR:27.0; CI: 5.67–179.65; p < 0.001) and ST101 (OR: 17.2; CI: 2.45–350.40; p = 0.01) were found to be predictors of 30-day mortality. Even the neutrophil uptake of kfu+-ybtS+ ColR-Kp was significantly higher than kfu--ybtS- ColR-Kp (phagocytosis rate: 78% vs. 65%, p < 0.001), and the kfu+-ybtS+ ColR-Kp survived more than kfu--ybtS- ColR-Kp (median survival index: 7.90 vs. 4.22; p = 0.001). The kfu+-ybtS+ ColR-Kp stimulated excessive NET formation. Iron uptake systems in high-risk clones of colistin-resistant K. pneumoniae enhance the success of survival against the neutrophil phagocytic defense and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be a promising approach for the treatment of colistin-resistant high-risk clones of K. pneumoniae infections.

Objective: It has been shown that clonal mutations occur in hematopoietic stem cells with advancing age and increase the risk of death due to atherosclerotic vascular diseases, similarly to myeloproliferative neoplasms. Endothelial cells (ECs) and hematopoietic stem cells develop from common stem cells called hemangioblasts in the early embryonic period. However, the presence of hemangioblasts in the postnatal period is controversial. In this study, JAK2 gene variants were examined in patients with atherosclerotic carotid disease and without any hematological malignancies. Materials and Methods: Ten consecutive patients (8 men and 2 women) with symptomatic atherosclerotic carotid stenosis were included in this study. ECs (CD31+CD45-) + CD45- ) were separated from tissue samples taken by carotid endarterectomy.JAK2variants were JAK2 variants were examined in ECs, peripheral blood mononuclear cells, and oral epithelial cells of the patients with next-generation sequencing. Results: The median age of the patients was 74 (range: 58-80) years and the median body mass index value was 24.44 (range: 18.4230.85) kg/m2. 2 . Smoking history was present in 50%, hypertension in 80%, diabetes in 70%, and ischemic heart disease in 70% of the cases. The JAK2 V617F mutation was detected in the peripheral blood mononuclear cells of 3 of the 10 patients, and 2 patients also had the JAK2 V617F mutation in their ECs. The JAK2 V617F mutation was not found in the oral epithelial cells of any of the patients. Conclusion: In this study, for the first time in the literature, we showed that the JAK2 V617F mutation was found somatically in both peripheral blood cells and ECs in patients with atherosclerosis. This finding may support that ECs and hematopoietic cells originate from a common clone or that somatic mutations can be transmitted to ECs by other mechanisms. Examining the molecular and functional changes caused by the JAK2 V617F mutation in ECs may help open a new avenue for treating atherosclerosis.

COVID-19 is caused by SARS-CoV-2 from the Coronaviridae family, Orthocoronaviridae sub family, Betacoronavirus genus, and Sarbecovirus subfamily (1). Cytokines and chemokines have been essential in the immune response against coronaviruses (2). First reports investigating clinical features of COVID-19 showed that serum levels of interleukin (IL)-2, IL-7, IL-10, granulocyte colony-stimulating factor (GSCF), IP10 (CXCL10),

While CD20 was initially characterized as a B cell–specific marker, its expression on memory T cells has expanded our understanding of this molecule’s distribution and function. Here, we identify a previously unrecognized CD20-expressing NK cell population and demonstrate its functional significance. CD56+CD20+ NK cells exhibit hallmarks of cellular activation, including elevated NKp46, CD69, and CD137 expression, enhanced proliferative capacity, and increased production of inflammatory cytokines (IFN-γ, GM-CSF, TNF-α, IL-10). Functional analyses revealed enhanced cytotoxicity against K562 targets, correlating with increased expression of cytolytic mediators including granzymes A, B, and K, perforin, FASL, and TRAIL. Single-cell transcriptional profiling demonstrated that MS4A1-expressing NK cells possess a distinct molecular signature characterized by elevated granzyme K expression and memory-like features. These cells preferentially localize to secondary lymphoid organs and accumulate in inflammatory tissues. Notably, CD56+CD20+ NK cells are enriched in multiple inflammatory conditions, including multiple sclerosis, autoimmune hepatitis, hepatitis B infection, hepatocellular carcinoma, and lung cancer. Treatment with rituximab depletes this population, suggesting potential therapeutic implications. Our findings establish CD20+ NK cells as a functionally distinct lymphocyte subset with enhanced effector capabilities and tissue-homing properties, providing new insights into immune regulation in inflammatory diseases.

Summary: Here we proposed the hypothesis that hypervirulent colistin resistant K.pneumoniae (ColR-Kp) exhibit high number of virulence factors and have enhanced survival capacity against neutrophil activity. We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive infections. The patients infected with hypervirulent ST101 and ST395 ColR-Kp had higher 30-day mortality (58%, p=0.005 and 75%, p=0.003, respectively. The yersiniabactin biosynthesis gene (ybtS) and ferric uptake operon associated gene (kfu) were significantly higher in ST101 (99%, p=<0.001) and in ST395 (94%, p<0.012). Being in ICU (OR: 7.9; CI: 1.43-55.98; p=0.024), kfu (OR:27.0; CI:5.67-179.65; p<0.001) and ST101 (OR: 17.2; CI: 2.45-350.40; p=0.01) were found to be predictors of 30-day mortality. The uptake of kfu ⁺ -ybtS ⁺ ColR-Kp by neutrophils was significantly higher than kfu ^- -ybtS ^- ColR-Kp (78% vs 65%, p<0.001). However, kfu ⁺ -ybtS ⁺ ColR-Kp were more resistant to the killing activity of neutrophils than negative ones (7.90 vs 4.22; p=0.001). The kfu ⁺ -ybtS ⁺ ColR-Kp stimulated excessive NET formation while the NET’s against kfu ^- -ybtS ^- ColR-Kp were weak and rare. Iron uptake systems enhance successful survival of K.pneumoniae against neutrophil phagocytic defense, and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be a promising approach for treatment of hypervirulent K.pneumoniae infections.