Chronic allergic asthma is characterized by Th2-typed inflammation, and contributes to airway remodeling and the deterioration of lung function. However, the initiating factor that links airway inflammation to remodeling is unknown. Thymic stromal lymphopoietin (TSLP), an epithelium-derived cytokine, can strongly activate lung dendritic cells (DCs) through the TSLP-TSLPR and OX40L-OX40 signaling pathways to promote Th2 differentiation. To determine whether TSLP is the underlying trigger of airway remodeling in chronic allergen-induced asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM) extracts for up to 5 consecutive weeks. We showed that repeated respiratory exposure to HDM caused significant airway eosinophilic inflammation, peribronchial collagen deposition, goblet cell hyperplasia, and airway hyperreactivity (AHR) to methacholine. These effects were accompanied with a salient Th2 response that was characterized by the upregulation of Th2-typed cytokines, such as IL-4 and IL-13, as well as the transcription factor GATA-3. Moreover, the levels of TSLP and transforming growth factor beta 1 (TGF-β1) were also increased in the airway. We further demonstrated, using the chronic HDM-induced asthma model, that the inhibition of Th2 responses via neutralization of TSLP with an anti-TSLP mAb reversed airway inflammation, prevented structural alterations, and decreased AHR to methacholine and TGF-β1 level. These results suggest that TSLP plays a pivotal role in the initiation and persistence of airway inflammation and remodeling in the context of chronic allergic asthma.

Serum resistance is a poorly understood but common trait of some difficult-to-treat pathogenic strains of bacteria. Here, we report that glycine, serine and threonine catabolic pathway is down-regulated in serum-resistant Escherichia coli , whereas exogenous glycine reverts the serum resistance and effectively potentiates serum to eliminate clinically-relevant bacterial pathogens in vitro and in vivo. We find that exogenous glycine increases the formation of membrane attack complex on bacterial membrane through two previously unrecognized regulations: 1) glycine negatively and positively regulates metabolic flux to purine biosynthesis and Krebs cycle, respectively. 2) α-Ketoglutarate inhibits adenosine triphosphate synthase, which in together promote the formation of cAMP/CRP regulon to increase the expression of complement-binding proteins HtrE, NfrA, and YhcD. The results could lead to effective strategies for managing the infection with serum-resistant bacteria, an especially valuable approach for treating individuals with weak acquired immunity but a normal complement system.

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Multidrug-resistant Escherichia coli metabolomes are reprogrammed by glutamine to be sensitive to ampicillin in vitro and in vivo.

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ObjectiveTo investigate the prevalence and trends of sensitisation to common aeroallergens among outpatients with allergic rhinitis (AR) in Guangzhou, China, over the past decade.DesignA retrospective study; linear-by-linear association and simple linear regression were used to determine the trends in the prevalence of aeroallergen sensitisation.SettingOne grade-A hospital in Guangzhou, the largest city in southern China.ParticipantsA total of 5486 patients (2297 males and 2489 females) who visited the ear, nose and throat outpatient clinic, from January 2005 to December 2014, were enrolled. All patients who presented with nasal hyper-reactive symptoms and who completed serological allergy testing, measuring specific IgE (sIgE) in the serum, were included. Among them, 4085 participants (2269 males and 1816 females) were diagnosed as being patients with AR.Outcome measuresPrevalence and trends of sensitisation to various types of aeroallergens were assessed.ResultsThe overall prevalence of sIgE-mediated sensitisation to aeroallergens in these patients with AR were as follows: 84.4% for house dust mites (HDMs), 23.4% for pet allergens, 21.1% for cockroaches, 9.1% for mould allergens, 7.7% for tree pollen and 6.0% for weed pollen. When all patients with nasal hyper-reactivity were stratified by decade of age, increasing age was associated with a decrease in sIgE positivity by ∼5.13% (95% CI −7.28% to −2.98%, p<0.01). Within the past decade, the prevalence of sensitisation to pet allergens in patients with AR increased at an annual rate of 1.3% (95% CI 0.85% to 1.67%, p<0.01).ConclusionsThis study demonstrated that HDMs comprised the most common aeroallergen in Guangzhou. The prevalence of sensitisation to aeroallergens decreased with increasing age. During the past decade, the prevalence of sensitisation to pet allergens showed an upward trend, suggesting an urgent need for its prevention and treatment.

Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive biomarkers for BPD. However, the roles of exosomes and EXO-miRNAs from umbilical cord blood of BPD infants in regulating angiogenesis are yet to be elucidated. In this study, we showed that umbilical cord blood-derived exosomes from BPD infants impaired angiogenesis in vitro. Next-generation sequencing of EXO-miRNAs from preterm infants without (NBPD group) or with BPD (BPD group) uncovered a total of 418 differentially expressed (DE) EXO-miRNAs. These DE EXO-miRNAs were primarily enriched in cellular function-associated pathways including the PI3K/Akt and angiogenesis-related signaling pathways. Among those EXO-miRNAs which are associated with PI3K/Akt and angiogenesis-related signaling pathways, BPD reduced the expression of hsa-miR-103a-3p and hsa-miR-185-5p exhibiting the most significant reduction (14.3% and 23.1% of NBPD group, respectively); BPD increased hsa-miR-200a-3p expression by 2.64 folds of the NBPD group. Furthermore, overexpression of hsa-miR-103a-3p and hsa-miR-185-5p in normal human umbilical vein endothelial cells (HUVECs) significantly enhanced endothelial cell proliferation, tube formation, and cell migration, whereas overexpressing hsa-miR-200a-3p inhibited these cellular responses. This study demonstrates that exosomes derived from umbilical cord blood of BPD infants impair angiogenesis, possibly via DE EXO-miRNAs, which might contribute to the development of BPD.

Infections with Pseudomonas aeruginosa have become a real concern among hospital-acquired infections, especially in cystic fibrosis patients and immunocompromised individuals. Control of the pathogen is challenging due to antibiotic resistance.