Exogenous Interleukin-37 Alleviates Hepatitis with Reduced Dendritic Cells and Induced Regulatory T Cells in Acute Murine Cytomegalovirus Infection.

Human cytomegalovirus (HCMV) infection is globally distributed, and the liver is one of the major targeting organs. So far, the mechanisms for cell and organ damage have not fully been elucidated and the treatments for the infection are mainly at symptoms. IL-37 has shown a protective role in certain inflammatory diseases. In the present study, potential protective effect of exogenous IL-37 on murine cytomegalovirus- (MCMV-) infected hepatitis was evaluated through analyses of serum transaminases, the liver histopathology and cytokine expression, and functional state of dendritic cells (DCs) and regulatory T cells (Tregs). These analyses showed a significant decrease in serum transaminase levels and a lower Ishak histopathologic score at the early stage of MCMV-infected mice with exogenous IL-37 pretreatment. The frequencies of MHC-Ⅱ, CD40, CD80, and CD86 positive DCs in the liver and spleen were decreased significantly at 7 days postinfection (dpi) in MCMV-infected mice with IL-37 pretreatment when compared with those without the pretreatment, while the total number of DCs in the liver was reduced in IL-37-pretreated mice. The induction of Tregs in the spleen was enhanced at dpi 3 with IL-37 pretreatment in MCMV-infected mice. The mRNA expression levels of cytokines in the liver were decreased significantly (IL-1ß, IL-6, IL-10, IL-4) or to some extent (TGF-ß and TNF-α). The present study suggested that exogenous IL-37 can alleviate MCMV-infected hepatitis, likely through reduced DCs and induced Tregs with a weaker cytokine storm, demonstrating its potential value in clinical management for HCMV-infected hepatitis.

Disease-Associated Gut Microbiota Reduces the Profile of Secondary Bile Acids in Pediatric Nonalcoholic Fatty Liver Disease.

Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen Escherichia coli that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids.

Uptrend prevalence of varicella parallel with low serum antibodies and low second-dose rate among children 10-14 years old in Wenzhou, China.

In recent years, the incidence of varicella cases is rising, and outbreaks of varicella are frequently being reported worldwide. Our study aims to analyze the association between the varicella incidence and serum antibody level in the post-vaccine era. We retrieved and analyzed the incidence and prevalence data for children age 1-14 years in Wenzhou, China during 2010-2018. A cross-sectional seroepidemiology analysis was carried out in a series of 168 general healthy children age 1-14 years as well as children at a varicella outbreak in Wenzhou. Our data showed a significant surge in the incidence and prevalence of varicella in children aged 10-14 years in 2017 and 2018 while they were kept relatively stable in 2010-2016. The seroepidemiological analysis revealed a 7.3-fold significantly higher level of serum varicella IgG in healthy control students who exposed at the outbreak than that in general healthy children (median 523.5 vs. 71.7 mIU/mL, p < .01). The children 10-14 years old had the lowest rate of second-dose vaccination among the three age classes (7%, 41%, and 65% in 10-14, 5-9, and 2-4 age class, respectively), and children 5-9 years old who received the second dose had a higher level of serum protective IgG than those who did not (254.7 vs 98 mIU/mL, p = .06). The findings from the present study warn a two-dose vaccine schedule to reduce the climbing incidence and prevalence observed in the older children and suggest a higher serum IgG threshold for effective protection of children from the varicella outbreak.