Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels and chronic low-grade inflammation. It shows a strong association with obesity and immune dysfunction, which makes T2DM patients more susceptible to infectious diseases. NK cells play an important role in pathogen control and tumor surveillance. However, whether NK cell distribution and functional status are altered in T2DM is unclear. To address this issue, we compared surface receptor expression and cytokine production between peripheral blood NK cells from 90 T2DM patients and 62 age- and sex-matched healthy controls. We found a significantly lower frequency and absolute number of NK cells in patients than in controls. Interestingly, the expression of inhibitory receptor Tim-3 was significantly increased, while the expression of the activating receptor NKG2D was significantly decreased, in T2DM NK cells. Both TNF-α secretion and degranulation capacity (evidenced by CD107a expression) were dampened in NK cells from patients. The expression of Tim-3 on NK cells correlated positively with both HbA1c and fasting blood glucose levels and negatively with the percentage and absolute number of total NK cells and was associated with increased NK cell apoptosis. In addition, Tim-3 expression on NK cells negatively correlated with TNF-α production, which could be restored by blocking Galectin-9/Tim-3 pathway. Our results suggest that NK cell dysfunction secondary to augmented Tim-3 expression occurs in T2DM patients, which may partly explain their increased susceptibility to cancer and infectious disease.

The pathophysiology of acute respiratory distress syndrome (ARDS) involves cytokine storms, alveolar-capillary barrier destruction, and fibrotic progression. Pulmonary interstitial fibrosis is an important factor affecting the prognosis of ARDS patients. Endothelial-to-mesenchymal transition (EndMT) plays an important role in the development of fibrotic diseases, and the occurrence of EndMT has been observed in experimental models of LPS-induced acute lung injury (ALI). Apelin is an endogenous active polypeptide that plays an important role in maintaining endothelial cell homeostasis and inhibiting fibrotic progression in various diseases. However, whether apelin attenuates EndMT in ALI and post-ALI pulmonary fibrosis remains unclear. We analyzed the serum levels of apelin-13 in patients with sepsis-associated ARDS to examine its possible clinical value. A murine model of LPS-induced pulmonary fibrosis and an LPS-challenged endothelial cell injury model were used to analyze the protective effect and underlying mechanism of apelin-13. Mice were treated with apelin-13 by i.p. injection, and human pulmonary microvascular endothelial cells were incubated with apelin-13 in vitro. We found that the circulating apelin-13 levels were significantly elevated in sepsis-associated ARDS patients compared with healthy controls. Our study also confirmed that LPS induced EndMT progression and pulmonary fibrosis, which were characterized by decreased CD31 expression and increased α-smooth muscle actin expression and collagen deposition. LPS also stimulated the production of transforming growth factor β1 and activated the Smad signaling pathway. However, apelin-13 treatment significantly attenuated these changes. Our findings suggest that apelin-13 may be a novel biomarker in patients with sepsis-associated ARDS. These results demonstrate that apelin-13 ameliorates LPS-induced EndMT and post-ALI pulmonary fibrosis by suppressing transforming growth factor β1 signaling.

Purpose Klebsiella pneumoniae ( K. pneumoniae ) is a Gram-negative bacterium that is predominantly associated with liver abscesses in global diabetic patients. High levels of glucose in the surrounding of K. pneumonia increase its pathogenicity including capsular polysaccharide (CPS) and fimbriae. Other important virulent factors include outer membrane protein A (ompA) and regulator mucoid phenotype A (rmpA). The objective of this investigation was to elucidate the effects of high glucose on rmpA and ompA gene expression and serum resistance of K. pneumoniae causing liver abscess. Patients and Methods The clinical history of 57 patients suffering from K. pneumoniae -caused liver abscesses (KLA) was acquired and their clinical and laboratory manifestations in the presence or absence of diabetes were analyzed. The antimicrobial susceptibility, serotypes, and virulence genes were tested. Clinical isolates of 3 serotype-K1 hypervirulent K. pneumoniae (hvKP) were used to detect the effect of exogenous high glucose on rmpA, ompA , and clbB genes expression, and bacterial serum resistance. Results KLA patients with diabetes showed higher C-reactive protein (CRP) compared to non-diabetic KLA patients. Furthermore, the diabetic group showed increased incidences of sepsis and invasive infections, and their length of hospital stay was also prolonged. Pre-incubation of K. pneumoniae in high glucose (0.5%) concentration up-regulated rmpA, ompA , and clbB genes expression. However, cAMP supplementation, which was inhibited by environmental glucose, reversed the increase of rmpA and ompA in a cAMP-dependent manner. Moreover, hvKP strains incubated in high glucose also exhibited enhanced protection from serum killing. Conclusion High glucose levels reflected by poor glycemic control has increased gene expression of rmpA and ompA in hvKP by the cAMP signaling pathway and enhanced its resistance to serum killing, thus providing a new and reasonable explanation for the high incidences of sepsis and invasive infections in KLA patients with diabetes.

Type 2 diabetes mellitus (T2DM) is associated with increased incidence and mortality of many cancers and infectious diseases. CD3 + CD56 + NKT-like cells play pivotal roles in tumor surveillance and infection control. However, little is known about potential alterations in circulating NKT-like cells in T2DM patients. In this study, we found that the frequency and absolute counts of circulating NKT-like cells were significantly lower in patients with T2DM compared to healthy volunteers. Moreover, in T2DM patients, NKT-like cells were impaired in their production of IFN-γ and TNF-α as well as degranulation capacity. The expression of activating receptor NKG2D was markedly decreased on NKT-like cells in T2DM patients, while the expression of inhibitory receptors Tim-3 and LAG-3 was upregulated. In detail, Tim-3 + NKT-like cells expressed higher LAG-3 and less IFN-γ and TNF-α compared to Tim-3 -NKT-like cells. Importantly, we further found that the expression of Tim-3 in NKT-like cells from T2DM patients correlated positively with glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels, as well as with diabetes duration. In conclusion, these results indicate that NKT-like cells from T2DM patients display an exhausted phenotype and reduced functionality. Moreover, Tim-3 expression on NKT-like cells likely serves a novel biomarker for duration of T2DM.

Background Tsukamurella is an environmental saprophyte that potentially causes various infections in humans. It has been reported to cause rare opportunistic infections in immunocompromised patients or patients with indwelling foreign bodies. Case Presentation We report a case of continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis caused by Tsukamurella inchonensis ( T. inchonensis ). The patient was admitted to our hospital while demonstrating a cloudy peritoneal dialysate. Peritoneal fluid sample culturing yielded yellow-greyish, dry and membrane-like colonies. Gram staining showed straight, gram-positive rods. The organism was identified to be Tsukamurella species by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). It was then characterized to be homologous to T. inchonensis in the GenBank database by 16S Ribosomal RNA Sequencing. The strain was susceptible to quinolones, carbapenems and linezolid, but intermediately resistant to vancomycin in drug susceptibility testing. Eventually, the peritonitis was controlled with meropenem and the patient discharged from the hospital. Conclusion Here, we describe the first case of CAPD-related peritonitis caused by T. inchonensis in China. Importantly, T. inchonensis show resistance to cephalosporins and heterogeneous resistance to vancomycin, guideline-based empiric therapy occasionally fails. Further analyses of similar cases are required to understand the characteristics and formulate appropriate therapy regimen for T. inchonensis infections.