DDX20 positively regulates the interferon pathway to inhibit viral infection.

The DEAD-box (DDX) family comprises RNA helicases characterized by the conserved sequence D(Asp)-E(Glu)-A(Ala)-D(Asp), participating in various RNA metabolism processes. Some DDX family members have been identified for their crucial roles in viral infections. In this study, RNAi library screening of the DDX family unveiled the antiviral activity of DDX20. Knockdown of DDX20 enhanced the replication of viruses such as vesicular stomatitis virus (VSV) and herpes simplex virus type I (HSV-1), while overexpression of DDX20 significantly diminished the replication level of these viruses. Mechanistically, DDX20 elevated the phosphorylation level of IRF3 induced by external stimuli by facilitating the interaction between TBK1 and IRF3, thereby promoting the expression of IFN-ß. The increased IFN-ß production, in turn, upregulated the expression of interferon-stimulated genes (ISGs), including Cig5 and IFIT1, thereby exerting the antiviral effect. Finally, in an in vivo infection study, Ddx20 gene-deficient mice exhibited increased susceptibility to viral infection. This study provides new evidence that DDX20 positively modulates the interferon pathway and restricts viral infection.

Housekeeping U1 snRNA facilitates antiviral innate immunity by promoting TRIM25-mediated RIG-I activation.

U1 small nuclear RNA (snRNA) is an abundant and evolutionarily conserved 164-nucleotide RNA species that functions in pre-mRNA splicing, and it is considered to be a housekeeping non-coding RNA. However, the role of U1 snRNA in regulating host antiviral immunity remains largely unexplored. Here, we find that RNVU1-18, a U1 pseudogene, is significantly upregulated in the host infected with RNA viruses, including influenza and respiratory syncytial virus. Overexpression of U1 snRNA protects cells against RNA viruses, while knockdown of U1 snRNA leads to more viral burden in vitro and in vivo. Knockout of RNVU1-18 is sufficient to impair the type I interferon-dependent antiviral innate immunity. U1 snRNA is required to fully activate the retinoic acid-inducible gene I (RIG-I)-dependent antiviral signaling, since it interacts with tripartite motif 25 (TRIM25) and enhances the RIG-I-TRIM25 interaction to trigger K63-linked ubiquitination of RIG-I. Our study reveals the important role of housekeeping U1 snRNA in regulating host antiviral innate immunity and restricting RNA virus infection.

The chemerin-CMKLR1 axis in keratinocytes impairs innate host defense against cutaneous Staphylococcus aureus infection.

The skin is the most common site of Staphylococcus aureus infection, which can lead to various diseases, including invasive and life-threatening infections, through evasion of host defense. However, little is known about the host factors that facilitate the innate immune evasion of S. aureus in the skin. Chemerin, which is abundantly expressed in the skin and can be activated by proteases derived from S. aureus, has both direct bacteria-killing activity and immunomodulatory effects via interactions with its receptor CMKLR1. Here, we demonstrate that a lack of the chemerin/CMKLR1 axis increases the neutrophil-mediated host defense against S. aureus in a mouse model of cutaneous infection, whereas chemerin overexpression, which mimics high levels of chemerin in obese individuals, exacerbates S. aureus cutaneous infection. Mechanistically, we identified keratinocytes that express CMKLR1 as the main target of chemerin to suppress S. aureus-induced IL-33 expression, leading to impaired skin neutrophilia and bacterial clearance. CMKLR1 signaling specifically inhibits IL-33 expression induced by cell wall components but not secreted proteins of S. aureus by inhibiting Akt activation in mouse keratinocytes. Thus, our study revealed that the immunomodulatory effect of the chemerin/CMKLR1 axis mediates innate immune evasion of S. aureus in vivo and likely increases susceptibility to S. aureus infection in obese individuals.

Intervention with ICOSL Antibodies Alleviates Inflammatory Infiltrations in Mice with Neutrophilic Asthma.

Background: Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation. Objective: To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma. Methods: Female BALB/c mice were randomly assigned to different groups. They were then injected with ovalbumin (OVA)/lipopolysaccharides (LPS) to induce neutrophilic asthma. The mice were then treated with either anti-ICOSL (the I group), control IgG (the G group), or no treatment (the N group). Additionally, a control group of mice received vehicle PBS and was labeled as the C group (n=6 per group). One day after the last allergen exposure, cytokine levels were measured in plasma and bronchoalveolar lavage fluid (BALF) using ELISA. After analyzing and categorizing BALF cells, the lung tissues were examined histologically and immunohistochemically. Results: Administering anti-ICOSL resulted in a significant decrease in the total number of inflammatory infiltrates and neutrophils found in BALF. Moreover, it led to a decrease in the levels of interleukin (IL)-6, IL-13, and IL-17 in both BALF and plasma. Additionally, there was an increase in IFN-γ levels in the BALF of asthmatic mice (p<0.05 for all). Treatment with anti-ICOSL also reduced lung interstitial inflammation, mucus secretion, and ICOSL expression in asthmatic mice. Conclusion: The treatment of anti-ICOSL effectively improved lung interstitial inflammation and mucus secretion in mice with neutrophilic asthma by restoring the balance of Th1/Th2/Th17 responses. These findings indicate that blocking the ICOS/ICOSL signaling could be an effective way to manage neutrophilic asthma.

FAP expression in adipose tissue macrophages promotes obesity and metabolic inflammation.

Adipose tissue macrophages (ATM) are key players in the development of obesity and associated metabolic inflammation which contributes to systemic metabolic dysfunction. We here found that fibroblast activation protein α (FAP), a well-known marker of cancer-associated fibroblast, is selectively expressed in murine and human ATM among adipose tissue-infiltrating leukocytes. Macrophage FAP deficiency protects mice against diet-induced obesity and proinflammatory macrophage infiltration in obese adipose tissues, thereby alleviating hepatic steatosis and insulin resistance. Mechanistically, FAP specifically mediates monocyte chemokine protein CCL8 expression by ATM, which is further upregulated upon high-fat-diet (HFD) feeding, contributing to the recruitment of monocyte-derived proinflammatory macrophages with no effect on their classical inflammatory activation. CCL8 overexpression restores HFD-induced metabolic phenotypes in the absence of FAP. Moreover, macrophage FAP deficiency enhances energy expenditure and oxygen consumption preceding differential body weight after HFD feeding. Such enhanced energy expenditure is associated with increased levels of norepinephrine (NE) and lipolysis in white adipose tissues, likely due to decreased expression of monoamine oxidase, a NE degradation enzyme, by Fap-/- ATM. Collectively, our study identifies FAP as a previously unrecognized regulator of ATM function contributing to diet-induced obesity and metabolic inflammation and suggests FAP as a potential immunotherapeutic target against metabolic disorders.

An update on respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections resulting in a significant burden worldwide, particularly in children and older adults. This collection calls for original research papers that advance our understanding of the epidemiology, evolution, diagnosis, clinical management, and prevention of RSV infections.

Etiology and clinical features of infection-associated plastic bronchitis in children.

OBJECTIVE: To investigate the etiological characteristics of plastic bronchitis (PB) caused by pulmonary infections in children and to identify any differences in the clinical features of PB cases caused by different pathogens. METHOD: We collected data on children diagnosed with PB and admitted to the Respiratory Department at Soochow University Children's Hospital between July 2021 and March 2023 utilizing electronic bronchoscopy. We analyzed clinical characteristics and the species of pathogens causing the illness in these children. RESULT: A total of 45 children were enrolled. The main clinical symptoms observed were cough (100%), fever (80%), shortness of breath (28.9%), and wheezing (20.0%). Pathogens were identified in 38 (84.4%) patients. Mycoplasma pneumoniae (MP) had the highest detection rate at 53.3%, followed by the Boca virus at 26.7%. MP-induced PB typically occurs in older children with an average age of 7.46 ± 2.36 years, with the main symptoms including high fever (85.7%) and local hyporespiration (42.9%). In contrast, Boca virus-induced PB tends to occur in younger children, with the main symptoms of moderate fever (54.5%), and wheezing (54.5%). The MP group exhibited a higher incidence of both internal and external pulmonary complications, including pleural effusion (42.9%), elevated aspartate aminotransferase (52.4%), lactic dehydrogenase (76.2%), and D-D dimer (90.5%). Conversely, the Boca virus group primarily showed pulmonary imaging of atelectasis (81.8%), with no pleural effusion. The average number of bronchoscopic interventions in the MP group was 2.24 ± 0.62, which was significantly higher than that required in the Boca virus group (1.55 ± 0.52). During the second bronchoscopy, 57.1% of children in the MP group still had visible mucus plugs, while none were observed in the Boca virus group. CONCLUSION: MP and Boca virus are the primary pathogens responsible for PB among children. The clinical manifestations of PB typically vary significantly based on the pathogen causing the condition.

DTX3L Enhances Type I Interferon Antiviral Response by Promoting the Ubiquitination and Phosphorylation of TBK1.

Studies already revealed that some E3 ubiquitin ligases participated in the immune response after viral infection by regulating the type I interferon (IFN) pathway. Here, we demonstrated that type I interferon signaling enhanced the translocation of ETS1 to the nucleus and the promoter activity of E3 ubiquitin ligase DTX3L (deltex E3 ubiquitin ligase 3L) after virus infection and thus increased the expression of DTX3L. Further experiments suggested that DTX3L ubiquitinated TBK1 at K30 and K401 sites on K63-linked ubiquitination pathway. DTX3L was also necessary for mediating the phosphorylation of TBK1 through binding with the tyrosine kinase SRC: both together enhanced the activation of TBK1. Therefore, DTX3L, being an important positive-feedback regulator of type I interferon, exerted a key role in antiviral response. IMPORTANCE Our present study evaluated DTX3L as an antiviral molecule by promoting IFN production and establishing an IFN-ß-ETS1-DTX3L-TBK1 positive-feedback loop as a novel immunomodulatory step to enhance interferon signaling and inhibit respiratory syncytial virus (RSV) infection. Our finding enriches and complements the biological function of DTX3L and provides a new strategy to protect against lung diseases such as bronchiolitis and pneumonia that develop with RSV.

The predictive values of soluble B7-DC in children with refractory mycoplasma pneumoniae pneumonia.

Background: Refractory mycoplasma pneumoniae pneumonia (RMPP) is a serious mycoplasma pneumoniae infection and is difficult to diagnose early. The levels of serum soluble B7-dendritic cell (sB7-DC) in children with mycoplasma pneumoniae pneumonia (MPP) were assessed to explore the clinical significance of sB7-DC levels in RMPP. Methods: A total of 65 patients with mycoplasma pneumoniae pneumonia (MPP) were enrolled in this study between January 2017 and December 2018. The patients were divided into the general mycoplasma pneumoniae pneumonia (GMPP) (n=30) and RMPP groups (n=35); the data of 20 normal children served as a control group (n=20). An enzyme-linked immunoassay kit was used to detect the expression of soluble B7-dendritic cell (sB7-DC) and other inflammatory factors. Binary logistic regression was performed to identify the independent predictors of RMPP. Receiver operating characteristic (ROC) curves were drawn to evaluate the value of each independent risk factor in the early diagnosis of RMPP. Results: The results showed that compared to the GMPP group, children in the RMPP group had a significantly longer hospital stay and had a significantly longer fever duration (P<0.05). The values of interferon-gamma (IFN-γ), interleukin 17 (IL-17), and sB7-DC in the RMPP group were significantly higher than those in the normal control and GMPP groups (all P<0.05). The results of the correlation analysis showed that sB7-DC was positively correlated with IFN-γ and IL-17 and these indicators could be used in combination to evaluate the severity of the disease. The binary logistic regression analysis identified IL-17 and sB7-DC as independent risk factors for RMPP (P<0.05). The ROC curve analysis showed that the cut-off values of IL-17 and sB7-DC were 309.6 pg/L and 1,109.7 pg/mL, respectively. The areas under the curve (AUCs) of IL-17 and sB7-DC were 0.741 and 0.794, respectively. The sensitivity of IL-17 to RMPP prediction was 83.3%, and the specificity was 62.9%. The sensitivity and specificity of sB7-DC to RMPP were 86.7% and 62.9%, indicating that sB7-DC had the highest predictive power for RMPP. Conclusions: The level of serum sB7-DC may play an important role in the early diagnosis of RMPP. Our research results provide a theoretical basis for the early diagnosis of RMPP.

Natural Morin-Based Metal Organic Framework Nanoenzymes Modulate Articular Cavity Microenvironment to Alleviate Osteoarthritis.

Osteoarthritis (OA) is always characterized as excessive reactive oxygen species (ROS) inside articular cavity. Mimicking natural metalloenzymes with metal ions as the active centers, stable metal organic framework (MOF) formed by natural polyphenols and metal ions shows great potential in alleviating inflammatory diseases. Herein, a series of novel copper-morin-based MOF (CuMHs) with different molar ratios of Cu2+ and MH were employed to serve as ROS scavengers for OA therapy. As a result, CuMHs exhibited enhanced dispersion in aqueous solution, improved biocompatibility, and efficient ROS-scavenging ability compared to MH. On the basis of H2O2-stimulated chondrocytes, intracellular ROS levels were efficiently declined and cell death was prevented after treated by Cu6MH (Cu2+ and MH molar ratio of 6:1). Meanwhile, Cu6MH also exhibited efficient antioxidant and anti-inflammation function by down-regulating the expression of IL6, MMP13, and MMP3, and up-regulating cartilage specific gene expression as well. Importantly, Cu6MH could repair mitochondrial function by increasing mitochondrial membrane potential, reducing the accumulation of calcium ions, as well as promoting ATP content production. In OA joint model, intra-articular (IA) injected Cu6MH suppressed the progression of OA. It endowed that Cu6MH might be promising nanoenzymes for the prevention and treatment of various inflammatory diseases.

Relationship between meteorological and environmental factors and acute exacerbation for pediatric bronchial asthma: Comparative study before and after COVID-19 in Suzhou.

Objective: Climate and environmental change is a well-known factor causing bronchial asthma in children. After the outbreak of coronavirus disease (COVID-19), climate and environmental changes have occurred. The present study investigated the relationship between climate changes (meteorological and environmental factors) and the number of hospitalizations for pediatric bronchial asthma in Suzhou before and after the COVID-19 pandemic. Methods: From 2017 to 2021, data on daily inpatients diagnosed with bronchial asthma at Children's Hospital of Soochow University were collected. Suzhou Meteorological and Environmental Protection Bureau provided daily meteorological and environmental data. To assess the relationship between bronchial asthma-related hospitalizations and meteorological and environmental factors, partial correlation and multiple stepwise regression analyses were used. To estimate the effects of meteorological and environmental variables on the development of bronchial asthma in children, the autoregressive integrated moving average (ARIMA) model was used. Results: After the COVID-19 outbreak, both the rate of acute exacerbation of bronchial asthma and the infection rate of pathogenic respiratory syncytial virus decreased, whereas the proportion of school-aged children and the infection rate of human rhinovirus increased. After the pandemic, the incidence of an acute asthma attack was negatively correlated with monthly mean temperature and positively correlated with PM2.5. Stepwise regression analysis showed that monthly mean temperature and O3 were independent covariates (risk factors) for the rate of acute asthma exacerbations. The ARIMA (1, 0, 0) (0, 0, 0) 12 model can be used to predict temperature changes associated with bronchial asthma. Conclusion: Meteorological and environmental factors are related to bronchial asthma development in children. The influence of meteorological and environmental factors on bronchial asthma may be helpful in predicting the incidence and attack rates.

Jumonji AT-rich interactive domain 1B promotes the growth of pancreatic tumors via the phosphatase and tensin homolog/protein kinase B signaling pathway.

[This retracts the article DOI: 10.3892/ol.2018.8618.].

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolates among children in Suzhou, China.

Background: Streptococcus pneumoniae (SP) is responsible for pneumococcal diseases with severe morbidity and mortality. High rates of drug resistance constitute serious public health concerns. Vaccination has proven to be an effective means of reducing disease burden. Epidemiological information of antibiotic susceptibilities and serotype distribution will be of great help to the management of pneumococcal infections. This study reported the serotype distribution and antibiotic resistance pattern of SP in hospitalized children in Suzhou during the years 2017-2018. The aim is to reduce pneumococcal resistance and guide vaccination. Methods: The clinical data of hospitalized children with SP were collected and analyzed. A total of 2,446 strains of SP were isolated from these patients. Serotypes were determined using the Quellung reaction. Antibiotic resistance was tested using the E-test diffusion method. Results: The non-susceptible rates of the isolates to penicillin, amoxicillin, and cefotaxime were 9.5%, 27.7%, and 27.2%, respectively. And 97.6% of SP isolates showed multidrug-resistant (MDR). The most common resistance pattern of non-invasive isolates was macrolides + sulfamethoxazole + clindamycin + tetracycline. The major serotypes of this resistance pattern were 6A, 23F, 6B, 19F, 15B. The most extensive resistance pattern of invasive isolates was macrolides + ß-lactams + sulfamethoxazole + clindamycin + tetracycline. The most common serotypes of the pattern were 19F, 19A, 6B, 23F, 6A. The most common serotypes were 19F (28.6%), 6B (11.9), 23F (11.2%), 6A (10.6%), and 19A (9.1%). In the isolates with MDR, the first five most common serotypes were 19F, non-vaccine serotype (NVT), 6B, 6A and 23F. Strains belonging to different serotypes exhibited distinct antimicrobial resistance patterns and were found to be associated with different diseases. The coverage rates of pneumococcal conjugate vaccine (PCV)7 and PCV13 in all isolates reached 60.4% (310/513) and 80.9% (415/513), respectively. Conclusions: The main serotypes of SP in Suzhou were 19F, 6B, 23F, 6A, and 19A. The use of PCV13 is beneficial to children in Suzhou.

Clinical characteristics and etiology of children with bronchiolitis before and during the COVID-19 pandemic in Suzhou, China.

Objective: We sought to compare the clinical characteristics and etiology of children with bronchiolitis in Suzhou before the pandemic of coronavirus disease 2019 (COVID-19) with those during the pandemic. Methods: Children who were hospitalized with bronchiolitis in the Department of Respiratory Disease, Children's Hospital of Soochow University were retrospectively enrolled over 3 consecutive years (2019, 2020, and 2021) from February 1 to January 31. Medical records were reviewed for etiology, clinical manifestations, and laboratory examination results. Results: The pathogen detection rate and the positive respiratory syncytial virus (RSV) detection rate were lowest in 2020 and highest in 2021. The rate of human rhinovirus detection in 2021 was higher than that in 2019 but similar to that in 2020. The RSV-positive rate differences among the 3 years varied by age group. Regarding the monthly distribution of RSV-positive cases over the 3-year study, all age groups showed a significant increase in the number of cases during the winter of 2021, and this increase started as early as October. With regard to clinical manifestations, the proportion of children presenting with stuffy nose rhinorrhea in 2021 [73.33% (165/225)] was greater than that in 2019 [48.61% (122/251)] and 2020 [57.06% (97/170)], while the proportion of children with gastrointestinal symptoms in 2021 [11.56% (26/225)] was smaller than that in 2019 [25.50% (64/251)] but similar to that in 2020 [17.06% (29/170)]. Conclusions: After the implementation of COVID-19 pandemic-related interventions, significantly lower pathogen detection and RSV-positive rates were observed in children with bronchiolitis in 2020. An upward trend in these rates was observed in 2021, coinciding with the relaxation of COVID-19 prevention measures. Strengthening infection control and surveillance systems is extremely important for future work.

The CARDS toxin of Mycoplasma pneumoniae induces a positive feedback loop of type 1 immune response.

Background: Within the past 3-5 years, Mycoplasma pneumoniae has become a major pathogen of community-acquired pneumonia in children. The pathogenic mechanisms involved in M. pneumoniae infection have not been fully elucidated. Methods: Previous protein microarray studies have shown a differential expression of CXCL9 after M. pneumoniae infection. Here, we conducted a hospital-based study to explore the clinical significance of the type 1 immune response inflammatory factors interferon (IFN)-γ and CXCL9 in patients with M. pneumoniae pneumonia (MPP). Then, through in vitro experiments, we explored whether CARDS toxin stimulated F-DCs (dendritic cells incubated with Flt3L) to promote Th-cell differentiation; we also investigated the IFN-γ-induced CXCL9 secretion pathway in macrophages and the role of CXCL9 in promoting Th1 cell migration. Results: The CXCL9 expression level was upregulated among patients with a higher fever peak, fever duration of greater than 7 days, an imaging manifestation of lobar or segmental, or combined pleural effusion (P<0.05). The peripheral blood levels of IFN-γ and CXCL9, which were higher in patients than in the healthy control group, were positively correlated with each other (r=0.502, P<0.05). In patients, the CXCL9 expression level was significantly higher in the bronchoalveolar lavage fluid (BALF) than in the peripheral blood, and the BALF CXCL9 expression level was higher than that in the healthy control group (all P<0.05). Our flow cytometry analysis revealed that M1-phenotype macrophages (CD16 + CD64 + CD163-) were predominant in the BALF from children with MPP. In in vitro experiments, F-DCs stimulated with CARDS toxin promoted the differentiation of CD4 + IFN-γ + Th (Th1) cells (P<0.05). Moreover, IFN-γ induced high levels of CXCL9 expression in M1-type macrophages in a dose-dependent and time-dependent manner. Additionally, macrophages transfection with STAT1-siRNA-1 downregulated the expression of CXCL9 (P<0.05), and CXCL9 promoted Th1 cell migration (P<0.05). Conclusions: Our findings suggest that CARDS toxin induces a type 1 immune response positive feedback loop during M. pneumoniae infection; this putative mechanism may be useful in future investigations of immune intervention approaches for M. pneumoniae pneumonia.

[Association of Haemophilus influenzae infection with environmental and climatic factors in Suzhou, China]. / è‹å·žåœ°åŒºæµæ„Ÿå—œè¡€æ†èŒæ„ŸæŸ“ä¸ŽçŽ¯å¢ƒæ°”å€™çš„ç›¸å ³å› ç´ åˆ†æž.

OBJECTIVES: To investigate the epidemiological characteristics of respiratory Haemophilus influenzae (HI) infection in children in Suzhou, China and its association with climatic factors and air pollutants. METHODS: The data on air pollutants and climatic factors in Suzhou from January 2016 to December 2019 were collected. Respiratory secretions were collected from 7 940 children with acute respiratory infection who were hospitalized during this period, and bacterial culture results were analyzed for the detection of HI. A stepwise regression analysis was used to investigate the association of HI detection rate with air pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) and climatic factors (monthly mean temperature, monthly mean humidity, monthly total rainfall, monthly total sunshine duration, and monthly mean wind speed). RESULTS: In 2016-2019, the 4-year overall detection rate of HI was 9.26% (735/7 940) among the children in Suzhou. The children aged <1 year and 1-<3 years had a significantly higher HI detection rate than those aged ≥3 years (P<0.01). The detection rate of HI in spring was significantly higher than that in the other three seasons, and the detection rate of HI in autumn was significantly lower than that in the other three seasons (P<0.001). The multiple linear regression analysis showed that PM10 and monthly mean wind speed were independent risk factors for the detection rate of HI: the detection rate of HI was increased by 0.86% for every 10 µg/m3 increase in the concentration of PM10 and was increased by 5.64% for every 1 m/s increase in monthly mean wind speed. Air pollutants and climatic factors had a lag effect on the detection rate of HI. CONCLUSIONS: HI is an important pathogen for acute respiratory infection in children in Suzhou and is prevalent in spring. PM10 and monthly mean wind speed are independent risk factors for the detection rate of HI.

MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1.

The role of micro RNAs (miRNAs) in asthma remains unclear. In this study, we examined the role of miRNA in targeting FOXO1 in asthma. Results showed that miR-493-5p was one of the differentially expressed miRNAs in the PBMCs of asthmatic children, and was also associated with Th cell differentiation. The miR-493-5p expression decreased significantly in the OVA-induced asthma mice than the control groups. The miR-493-5p mimic inhibited the expression of the IL-9, IRF4 and FOXO1, while the inhibitor restored these effects. Moreover, the Dual-Luciferase analysis results showed FOXO1 as a novel valid target of miR-493-5p. According to the rescue experiment, miR-493-5p inhibited Th9 cell differentiation by targeting FOXO1. Then the exosomes in association with the pathogenesis of asthma was identified. Various inflammatory cells implicated in asthmatic processes including B and T lymphocytes, DCs, mast cells, and epithelial cells can release exosomes. Our results demonstrated that the DC-derived exosomes can inhibit Th9 cell differentiation through miR-493-5p, thus DC-derived exosomal miR-493-5p/FOXO1/Th9 may serve as a potential therapeutic target in the development of asthma.

Protein Acetylation Going Viral: Implications in Antiviral Immunity and Viral Infection.

During viral infection, both host and viral proteins undergo post-translational modifications (PTMs), including phosphorylation, ubiquitination, methylation, and acetylation, which play critical roles in viral replication, pathogenesis, and host antiviral responses. Protein acetylation is one of the most important PTMs and is catalyzed by a series of acetyltransferases that divert acetyl groups from acetylated molecules to specific amino acid residues of substrates, affecting chromatin structure, transcription, and signal transduction, thereby participating in the cell cycle as well as in metabolic and other cellular processes. Acetylation of host and viral proteins has emerging roles in the processes of virus adsorption, invasion, synthesis, assembly, and release as well as in host antiviral responses. Methods to study protein acetylation have been gradually optimized in recent decades, providing new opportunities to investigate acetylation during viral infection. This review summarizes the classification of protein acetylation and the standard methods used to map this modification, with an emphasis on viral and host protein acetylation during viral infection.

PLK1 promotes cholesterol efflux and alleviates atherosclerosis by up-regulating ABCA1 and ABCG1 expression via the AMPK/PPARγ/LXRα pathway.

Polo-like kinase 1 (PLK1) is a serine/threonine kinase involving lipid metabolism and cardiovascular disease. However, its role in atherogenesis has yet to be determined. The aim of this study was to observe the impact of PLK1 on macrophage lipid accumulation and atherosclerosis development and to explore the underlying mechanisms. We found a significant reduction of PLK1 expression in lipid-loaded macrophages and atherosclerosis model mice. Lentivirus-mediated overexpression of PLK1 promoted cholesterol efflux and inhibited lipid accumulation in THP-1 macrophage-derived foam cells. Mechanistic analysis revealed that PLK1 stimulated the phosphorylation of AMP-activated protein kinase (AMPK), leading to activation of the peroxisome proliferator-activated receptor γ (PPARγ)/liver X receptor α (LXRα) pathway and up-regulation of ATP binding cassette transporter A1 (ABCA1) and ABCG1 expression. Injection of lentiviral vector expressing PLK1 increased reverse cholesterol transport, improved plasma lipid profiles and decreased atherosclerotic lesion area in apoE-deficient mice fed a Western diet. PLK1 overexpression also facilitated AMPK and HSL phosphorylation and enhanced the expression of PPARγ, LXRα, ABCA1, ABCG1 and LPL in the aorta. In summary, these data suggest that PLK1 inhibits macrophage lipid accumulation and mitigates atherosclerosis by promoting ABCA1- and ABCG1-dependent cholesterol efflux via the AMPK/PPARγ/LXRα pathway.