Fatty Acid Metabolism is Associated With Disease Severity After H7N9 Infection

Sun, Xin; Song, Lijia; Feng, Shuang; Li, Li; Heng, Yu; Wang, Qiaoxing; Wang, Xing; Hou, Zhili; Li, Xue; Liu, Yu; Zhang, Qiuyang; Li, Kuan; Cui, Chao; Wu, Junping; Qin, Zhonghua; Wu, Qi; Chen, Huaiyong

doi:10.1016/j.ebiom.2018.06.019

Cited by 33 publications

(34 citation statements)

References 60 publications

(70 reference statements)

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“…Third, the present findings are limited to patients without active respiratory infections. Alterations in metabolomic profile with lung infections is well realized [79][80][81]. Since patients with ACO are susceptible to infection [82,83], it would be worthwhile to investigate ACO metabolomic profiles with and without infections.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic fingerprinting and systemic inflammatory profiling of asthma COPD overlap (ACO)

et al. 2020

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Background: Asthma-COPD overlap (ACO) refers to a group of poorly studied and characterised patients reporting with disease presentations of both asthma and COPD, thereby making both diagnosis and treatment challenging for the clinicians. They exhibit a higher burden in terms of both mortality and morbidity in comparison to patients with only asthma or COPD. The pathophysiology of the disease and its existence as a unique disease entity remains unclear. The present study aims to determine whether ACO has a distinct metabolic and immunological mediator profile in comparison to asthma and COPD. Methods: Global metabolomic profiling using two different groups of patients [discovery (D) and validation (V)] were conducted. Serum samples obtained from moderate and severe asthma [n = 34(D); n = 32(V)], moderate and severe COPD [n = 30(D); 32(V)], ACO patients [n = 35(D); 40(V)] and healthy controls [n = 33(D)] were characterized using gas chromatography mass spectrometry (GC-MS). Multiplexed analysis of 25 immunological markers (IFN-γ (interferon gamma), TNF-α (tumor necrosis factor alpha), IL-12p70 (interleukin 12p70), IL-2, IL-4, IL-5, IL-13, IL-10, IL-1α, IL-1β, TGF-β (transforming growth factor), IL-6, IL-17E, IL-21, IL-23, eotaxin, GM-CSF (granulocyte macrophagecolony stimulating factor), IFN-α (interferon alpha), IL-18, NGAL (neutrophil gelatinase-associated lipocalin), periostin, TSLP (thymic stromal lymphopoietin), MCP-1 (monocyte chemoattractant protein-1), YKL-40 (chitinase 3 like 1) and IL-8) was also performed in the discovery cohort. Results: Eleven metabolites [serine, threonine, ethanolamine, glucose, cholesterol, 2-palmitoylglycerol, stearic acid, lactic acid, linoleic acid, D-mannose and succinic acid] were found to be significantly altered in ACO as compared with asthma and COPD. The levels and expression trends were successfully validated in a fresh cohort of subjects. Thirteen immunological mediators including TNFα, IL-1β, IL-17E, GM-CSF, IL-18, NGAL, IL-5, IL-10, MCP-1, YKL-40, IFNγ, IL-6 and TGF-β showed distinct expression patterns in ACO. These markers and metabolites exhibited significant correlation with each other and also with lung function parameters.

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Section: Discussionmentioning

confidence: 99%

Metabolomic fingerprinting and systemic inflammatory profiling of asthma COPD overlap (ACO)

et al. 2020

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“…Targeting the mTOR pathway as a means to reduce inflammation and promote recovery implicates host metabolism in the etiology of severe influenza disease, given the central role mTOR plays in nutrient sensing. Metabolic disruptions have been noted in local and systemic analyses of severe cases of influenza [25] and metabolic interventions have been shown to alter host response profiles in ways that could be protective or harmful depending on the infection context. For example, in mouse models of bacterial sepsis or influenza virus infection, glucose restriction had opposing effects, protecting against bacterial sepsis but exacerbating influenza-associated disease [26].…”

Section: How Influenza Triggers Ardsmentioning

confidence: 99%

Influenza virus-related critical illness: pathophysiology and epidemiology

2019

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Influenza virus affects the respiratory tract by direct viral infection or by damage from the immune system response. In humans, the respiratory epithelium is the only site where the hemagglutinin (HA) molecule is effectively cleaved, generating infectious virus particles. Virus transmission occurs through a susceptible individual’s contact with aerosols or respiratory fomites from an infected individual. The inability of the lung to perform its primary function of gas exchange can result from multiple mechanisms, including obstruction of the airways, loss of alveolar structure, loss of lung epithelial integrity from direct epithelial cell killing, and degradation of the critical extracellular matrix. Approximately 30–40% of hospitalized patients with laboratory-confirmed influenza are diagnosed with acute pneumonia. These patients who develop pneumonia are more likely to be < 5 years old, > 65 years old, Caucasian, and nursing home residents; have chronic lung or heart disease and history of smoking, and are immunocompromised. Influenza can primarily cause severe pneumonia, but it can also present in conjunction with or be followed by a secondary bacterial infection, most commonly by Staphylococcus aureus and Streptococcus pneumoniae . Influenza is associated with a high predisposition to bacterial sepsis and ARDS. Viral infections presenting concurrently with bacterial pneumonia are now known to occur with a frequency of 30–50% in both adult and pediatric populations. The H3N2 subtype has been associated with unprecedented high levels of intensive care unit (ICU) admission. Influenza A is the predominant viral etiology of acute respiratory distress syndrome (ARDS) in adults. Risk factors independently associated with ARDS are age between 36 and 55 years old, pregnancy, and obesity, while protective factors are female sex, influenza vaccination, and infections with Influenza A (H3N2) or Influenza B viruses. In the ICU, particularly during the winter season, influenza should be suspected not only in patients with typical symptoms and epidemiology, but also in patients with severe pneumonia, ARDS, sepsis with or without bacterial co-infection, as well as in patients with encephalitis, myocarditis, and rhabdomyolysis.

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“…Surfactant protein D (SP-D) specifically binds glycosylated pathogens, including SARS-CoV-1 8 . AEC2 fatty acid metabolism and LB ultrastructure are severely disrupted by the pandemic influenza strain H1N1 9 and the highly pathogenic H7N9 strain 10 . In spite of their importance in health and disease, many questions remain open about LB biogenesis, structure and secretion.…”

Section: Introductionmentioning

confidence: 99%

Post-correlation on-lamella cryo-CLEM reveals the membrane architecture of lamellar bodies

Klein

Wimmer

Winter

et al. 2020

Preprint

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Lamellar bodies (LBs) are surfactant rich organelles in alveolar type 2 cells. LBs disassemble into a lipid-protein network that reduces surface tension and facilitates gas exchange at the air-water interface in the alveolar cavity. Current knowledge of LB architecture is predominantly based on electron microscopy studies using disruptive sample preparation methods. We established a post-correlation on-lamella cryo-correlative light and electron microscopy approach for cryo-FIB milled lung cells to structurally characterize and validate LB identity in their unperturbed state using the well-established ABCA3-eGFP marker. In situ cryo-electron tomography revealed that LBs are composed of lipidic structures unique in organelle biology. We report open-ended membrane sheets frequently attached to the limiting membrane of LBs and so far undescribed dome-shaped protein complexes. We propose that LB biogenesis is driven by parallel membrane sheet import and the curvature of the limiting membrane to maximize lipid storage capacity.

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Fatty Acid Metabolism is Associated With Disease Severity After H7N9 Infection

Cited by 33 publications

References 60 publications

Metabolomic fingerprinting and systemic inflammatory profiling of asthma COPD overlap (ACO)

Metabolomic fingerprinting and systemic inflammatory profiling of asthma COPD overlap (ACO)

Influenza virus-related critical illness: pathophysiology and epidemiology

Post-correlation on-lamella cryo-CLEM reveals the membrane architecture of lamellar bodies

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