Although epidemiologic data strongly suggest a role for inhaled environmental pollutants in modulating the susceptibility to respiratory infection in humans, the underlying cellular and molecular mechanisms have not been well studied in experimental systems. The current study assessed the impact of inhaled diesel engine emissions (DEE) on the host response in vivo to a common pediatric respiratory pathogen, respiratory syncytial virus (RSV). Using a relatively resistant mouse model of RSV infection, prior exposure to either 30 microg/m3 particulate matter (PM) or 1,000 microg/m3 PM of inhaled DEE (6 h/d for seven consecutive days) increased lung inflammation to RSV infection as compared with air-exposed RSV-infected C57Bl/6 mice. Inflammatory cells in bronchoalveolar lavage fluid were increased in a dose-dependent manner with regard to the level of DEE exposure, concomitant with increased levels of inflammatory mediators. Lung histology analysis indicated pronounced peribronchial and peribronchiolar inflammation concordant with the level of DEE exposure during infection. Mucous cell metaplasia was markedly increased in the airway epithelium of DEE-exposed mice following RSV infection. Interestingly, both airway and alveolar host defense and immunomodulatory proteins were attenuated during RSV infection by prior DEE exposure. DEE-induced changes in inflammatory and lung epithelial responses to infection were associated with increased RSV gene expression in the lungs following DEE exposure. These findings are consistent with the concept that DEE exposure modulates the lung host defense to respiratory viral infections and may alter the susceptibility to respiratory infections leading to increased lung disease.

Clara cell secretory protein (CCSP) is synthesized by nonciliated bronchiolar cells in the lung and modulates lung inflammation to infection. To determine the role of CCSP in the host response to allergic airway disease, CCSP-deficient [(-/-)] mice were immunized twice with ovalbumin (Ova) and challenged by Ova (2 or 5 mg/m(3)) aerosol. After 2, 3, and 5 days of Ova aerosol challenge (6 h/day), airway reactivity was increased in CCSP(-/-) mice compared with wild-type [CCSP(+/+)] mice. Neutrophils were markedly increased in the bronchoalveolar lavage fluid of CCSP(-/-) Ova mice, coinciding with increased myeloperoxidase activity and macrophage inflammatory protein-2 levels. Lung histopathology and inflammation were increased in CCSP(-/-) compared with wild-type mice after Ova challenge. Mucus production, as assessed by histological staining, was increased in the airway epithelium of CCSP(-/-) Ova mice compared with that in CCSP(+/+) Ova mice. These data suggest a role for CCSP in airway reactivity and the host response to allergic airway inflammation and provide further evidence for the role of the airway epithelium in regulating airway responses in allergic disease.

SUMMARYDogs with immunoglobulin E (IgE) allergy for ragweed that are sensitized by intrapulmonary exposure to ragweed can be used to study the pulmonary immune response that is important in allergic asthma. Using this model, we tested the hypothesis that T lymphocytes are activated locally in the airways shortly after allergen exposure of the lungs. The airways of six allergic dogs and three non-allergic dogs were exposed to ragweed by segmental allergen challenge (SAC). T-cell subsets and T-cell activation in blood and bronchoalveolar lavage (BAL) fluid were measured by flow cytometry before SAC and at 4, 24 and 72 hr thereafter. SAC caused a statistically significant increase in the percentage of major histocompatibility complex (MHC) class II-positive CD4 and CD8 T cells in BAL fluid and a significant increase in the mean fluorescent activity of MHC class II from 4 hr after SAC onward. This activation was significantly different from that found in cells from lung lobes challenged with saline, or from lung lobes in non-allergic dogs challenged with ragweed. The percentage of CD45RA bright CD8 cells increased significantly in allergic dogs after both ragweed and saline challenges. This was significantly higher than in non-allergic dogs. We conclude that T-cell activation in the airways of dogs can be measured after in vivo activation of the cells by measuring MHC class II and CD45RA expression in BAL fluid T cells. Furthermore, in allergic dogs, T cells are activated locally in the lungs within 4 hr after exposure to ragweed allergen. These results suggest a role for T lymphocytes in the development of late-phase allergic reactions in the airways.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, yet as of currently, there is no disease-modifying therapy that could delay its progression. Paeonia lactiflora Pall. is the most frequently used herb in formulas for PD in Traditional Chinese Medicine and also a potential neuroprotective agent for neurodegenerative diseases, while its mechanisms remain poorly understood. In this study, we aim to explore the underlying mechanism of P. lactiflora in treating PD utilizing a network pharmacology approach.Methods: The protein targets of P. lactiflora ingredients and PD were first obtained from several databases. To clarify the key targets, a Protein-Protein-Interaction (PPI) network was constructed and analyzed on the String database, and then enrichment analysis was performed by the Metascape platform to determine the main Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Finally, the Ingredient-Target-Pathway (I-T-P) network was constructed and analyzed by Cytoscape software.Results: Six active ingredients of P. lactiflora (kaempferol, ß-sitosterol, betulinic acid, palbinone, paeoniflorin and (+)-catechin) as well as six core targets strongly related to PD treatment [AKT1, interleukin-6, CAT, Tumor necrosis factor (TNF), CASP3, and PTGS2] were identified. The main pathways were shown to involve neuroactive ligand-receptor interaction, Calcium signaling pathway, PI3-Akt signaling pathway, TNF signaling pathway, and apoptosis signaling pathway. The main biological process included the regulation of neurotransmitter levels.Conclusion:P. lactiflora may retard neurodegeneration by reducing neuroinflammation, inhibiting intrinsic and extrinsic apoptosis, and may improve motor and non-motor symptoms by regulating the levels of neurotransmitters. Our study has revealed the mechanism of P. lactiflora in the treatment of PD and may contribute to novel drug development for PD.

Dendritic cells (DCs) are readily infected by influenza viruses and play a crucial role in regulating host innate and adaptive immune responses to viral infection. The aims of this study are to characterize the dynamic changes in the numbers and maturation status of dendritic cells present in the lung and lung-associated lymph nodes (LALNs) in the model of a non-human primate (NHP) infected by influenza A virus (IAV). Cynomolgus macaques were infected with influenza A virus (H3N2) via bronchoscopy. Flow cytometry was used to analyze the DC numbers, maturation status and subsets during the time of acute infection (days 1, 2, 3, 4, 7) and the resolution phase (day 30). A dramatic increase in the numbers of influenza A virus-infected CD11c+CD14- myeloid dendritic cells (mDCs) and CD11c-CD123+ plasmacytoid dendritic cells (pDCs) were observed from day 1 to day 4 and peak up from day 7 post-infection. In lung and lung-associated lymph nodes, the numbers and maturation status of myeloid dendritic cells and plasmacytoid dendritic cells increased more slowly than those in the lung tissues. On day 30 post-infection, influenza A virus challenge increased the number of myeloid dendritic cells, but not plasmacytoid dendritic cells, compared with baseline. These findings indicate that dendritic cells are susceptible to influenza A virus infection, with the likely purpose of increasing mature myeloid dendritic cells numbers in the lung and lung and lung-associated lymph nodes, which provides important new insights into the regulation of dendritic cells in a non-human primate model.

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Evidence on the association between dietary patterns and sleep disorders is limited and controversial. In addition, studies evaluating the effect of dietary patterns on sleep disorders have seldom considered the critical role of obesity. We aimed to explore obesity-related dietary patterns and evaluate their impact on sleep disorders using data from the National Health and Nutrition Examination Survey 2005–2014. In total, 19,892 participants aged over 20 years with two-day dietary recalls were enrolled. Obesity-related dietary patterns explaining most variance in waist circumference and BMI simultaneously were extracted from twenty-six food groups by the using partial least squares method. Sleep disorder and sleep duration, which were defined by self-reported questions, were the primary and the secondary outcome, respectively. Generalized linear models were performed to estimate the association of sleep disorders and sleep duration with dietary patterns. Two types of dietary patterns were identified. The “high fats, refined grains, and meat” pattern was characterized by high intakes of solid fats, cured meat, potatoes, refined grains, meat, cheese, and added sugars. The “low whole grains, vegetables, and fruits” pattern was characterized by low intakes of oils, whole grains, nuts and seeds, milk, fruits, and several vegetables. Participants with the highest adherence to the “high fats, refined grains, and meat” pattern had a higher risk for sleep disorders (OR (95%CI): 1.43 (1.12, 1.84)) and shorter sleep duration (β (95%CI): −0.17 (−0.26, −0.08)) compared to those with the lowest adherence. The corresponding associations for the “low whole grains, vegetables, and fruits” pattern were only significant for sleep duration (β (95%CI): −0.26 (−0.37, −0.15)). Our results found that the dietary pattern characterized by high solid fats, cured meat, potatoes, refined grains, meat, cheese, and added sugars, was associated with a higher risk for sleep disorders and shorter sleep duration.

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