CD40L-Activated DC Promotes Th17 Differentiation and Inhibits Th2 Differentiation in Sepsis-Induced Lung Injury via cGAS-STING Signaling.

Immune hemostasis due to an infection plays a vital role in sepsis-induced multiple organ dysfunction. Dendritic cells (DC) and T helper (Th) cells are the key members of the immune system maintaining immune homeostasis. This study aimed to explore the effect and mechanism of CD40L on the activation of DC and activated DC-induced Th2/Th17 differentiation. A CD40L knockout and cecal ligation and puncture (CLP) mouse model was established via cecal ligation. HE staining was used to evaluate the pathological changes. The gene expressions were studied using quantitative real-time polymerase chain reaction (qRT-PCR), while a transwell system was used to perform the co-culture of DC and T-cells. Flow cytometry was performed to detect the subtype of T and DC cells. ELISA was used to assess the amount of inflammatory factors. CD40L was highly expressed in the plasma of CLP mice. Knock out of CD40L inhibited the activation of DC cell and Th17 differentiation while promoting the Th2 differentiation. The mechanistic investigations revealed that CD40L promoted the activation of cGAS-STING pathway. Rescue experiments indicated that CD40L mediated DC activation via cGAS-STING signaling. Moreover, co-culturing of CD and CD+4 T-cells demonstrated that silencing of CD40L in DC suppressed the DC activation and inhibited Th17 differentiation while promoting Th2 differentiation. These findings revealed a relationship between CD40L, DC activation, and Th2/Th17 differentiation balance in sepsis-induced acute lung injury for the first time. These findings are envisaged to provide novel molecular targets for sepsis-induced lung injury treatment.

Clinical warning of hemophagocytic syndrome caused by Epstein-Barr virus.

OBJECTIVES: This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1-3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). METHODS: The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects' clinical manifestations and laboratory tests were analyzed retrospectively. RESULTS: Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 µg/L, the sensitivity and specificity of D-Dimer was 88.90 and 90.20%, respectively. CONCLUSION: The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

The relationship between air quality and respiratory pathogens among children in Suzhou City.

OBJECTIVE: We studied the short-term effects of air pollutant concentrations in Suzhou City on respiratory infections in children of different age groups. METHODS: We employed clinical data from children hospitalized with respiratory infections at the Children's Hospital of Soochow University during 2014-2016, and air quality for Suzhou City covering the same period.We investigated the relationships between the air pollutant concentrations and respiratory tract infections in children by causative pathogen using time series models with lagged effects. RESULTS: The results of single-pollutant models showed that PM2.5, PM10, NO2, SO2 and CO had statistically significant associations with respiratory tract infections in children under 3 years, with the largest effect sizes at a lag of 3 weeks. Notably, the multi-pollutant model found PM2.5 was significantly associated with viral respiratory in children under 7 months, and bacterial respiratory infections in other age groups, while PM10 concentrations were associated with viral infections in preschool children. CONCLUSION: PM2.5, PM10 and NO2 are the main atmospheric pollutants in Suzhou. The associations between pollutant concentrations and viral and bacterial respiratory infections were stronger among children under 3 years than for older age group.s PM2.5 had the strongest influence on viral and Mycoplasma pneumoniae respiratory infections when multiple pollutants were tested together.