scholarly journals Upregulation of Human Endogenous Retroviruses in Bronchoalveolar Lavage Fluid of COVID-19 Patients

2021 ◽  
Author(s):  
Konstantina Kitsou ◽  
Anastasia Kotanidou ◽  
Dimitrios Paraskevis ◽  
Timokratis Karamitros ◽  
Aris Katzourakis ◽  
...  
Keyword(s):  
Risk Factor ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Important Risk Factor ◽  
Older Age ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Global Pandemic

SARS-CoV-2 emerged in late 2019 in China, causing a global pandemic. Severe COVID-19 is characterized by intensive inflammatory responses, and older age is an important risk factor for unfavorable outcomes.

scholarly journals Upregulation of Human Endogenous Retroviruses in Bronchoalveolar Lavage Fluid of COVID-19 Patients

2020 ◽  
Author(s):  
Konstantina Kitsou ◽  
Anastasia Kotanidou ◽  
Dimitrios Paraskevis ◽  
Timokratis Karamitros ◽  
Aris Katzourakis ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Endogenous Retroviruses ◽  
Apparent Difference ◽  
Blood Monocytes ◽  
Human Endogenous Retroviruses ◽  
Inflammatory Processes ◽  
Potential Link

Abstract BackgroundSevere COVID-19 pneumonia has been associated with the development of intense inflammatory responses during the course of infections with SARS-CoV-2. Given that Human Endogenous Retroviruses (HERVs) are known to be activated during and participate in inflammatory processes, we examined whether HERV dysregulation signatures are present in COVID-19 patients. ResultsBy comparing transcriptomes of Peripheral Blood Monocytes (PBMCs) and Bronchoalveolar Lavage Fluid (BALF) from patients and normal controls we have shown that HERVs are intensely dysregulated in BALF, but not in PBMCs. In particular, upregulation in the expression of multiple HERV families was detected in BALF samples of COVID-19 patients, with HERV-H being the most highly upregulated family among the families analysed. In addition, we compared the expression of HERVs in Human Bronchial Epithelial Cells (HBECs) without and after senescence induction in an oncogene-induced senescence model, in order to quantitatively measure changes in the expression of HERVs in bronchial cells during the processes of cellular senescence.ConclusionsThis apparent difference of HERV dysregulation between PBMCs and BALF warrants further studies in involvement of HERVs in inflammatory pathogenetic mechanisms as well as exploration of HERVs as potential biomarkers for disease progression. Furthermore, the increase in the expression of HERVs in senescent HBECs in comparison to non-induced HBECs provides a potential link for increased COVID-19 severity and mortality in aged populations.

scholarly journals Upregulation of Human Endogenous Retroviruses in Bronchoalveolar Lavage Fluid of COVID-19 Patients

2020 ◽  
Author(s):  
Konstantina Kitsou ◽  
Anastasia Kotanidou ◽  
Dimitrios Paraskevis ◽  
Timokratis Karamitros ◽  
Aris Katzourakis ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Endogenous Retroviruses ◽  
Apparent Difference ◽  
Blood Monocytes ◽  
Human Endogenous Retroviruses ◽  
Inflammatory Processes ◽  
Potential Link

Background: Severe COVID-19 pneumonia has been associated with the development of intense inflammatory responses during the course of infections with SARS-CoV-2. Given that Human Endogenous Retroviruses (HERVs) are known to be activated during and participate in inflammatory processes, we examined whether HERV dysregulation signatures are present in COVID-19 patients. Results: By comparing transcriptomes of Peripheral Blood Monocytes (PBMCs) and Bronchoalveolar Lavage Fluid (BALF) from patients and normal controls we have shown that HERVs are intensely dysregulated in BALF, but not in PBMCs. In particular, upregulation in the expression of multiple HERV families was detected in BALF samples of COVID-19 patients, with HERV-W being the most highly upregulated family among the families analysed. In addition, we compared the expression of HERVs in Human Bronchial Epithelial Cells (HBECs) without and after senescence induction in an oncogene-induced senescence model, in order to quantitatively measure changes in the expression of HERVs in bronchial cells during the processes of cellular senescence. Conclusions: This apparent difference of HERV dysregulation between PBMCs and BALF warrants further studies in involvement of HERVs in inflammatory pathogenetic mechanisms as well as exploration of HERVs as potential biomarkers for disease progression. Furthermore, the increase in the expression of HERVs in senescent HBECs in comparison to non-induced HBECs provides a potential link for increased COVID-19 severity and mortality in aged populations.

scholarly journals On Deep Landscape Exploration of COVID-19 Patients Cells and Severity Markers

2021 ◽  
Vol 12 ◽  
Author(s):  
Aarón Vázquez-Jiménez ◽  
Ugo Enrique Avila-Ponce De León ◽  
Meztli Matadamas-Guzman ◽  
Erick Andrés Muciño-Olmos ◽  
Yoscelina E. Martínez-López ◽  
...  
Keyword(s):  
Immune Response ◽  
Bronchoalveolar Lavage ◽  
Single Cell ◽  
Disease Severity ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Responses ◽  
Lavage Fluid ◽  
Supervised Machine Learning ◽  
Immune Memory ◽  
Clinical Responses

COVID-19 is a disease with a spectrum of clinical responses ranging from moderate to critical. To study and control its effects, a large number of researchers are focused on two substantial aims. On the one hand, the discovery of diverse biomarkers to classify and potentially anticipate the disease severity of patients. These biomarkers could serve as a medical criterion to prioritize attention to those patients with higher prone to severe responses. On the other hand, understanding how the immune system orchestrates its responses in this spectrum of disease severities is a fundamental issue required to design new and optimized therapeutic strategies. In this work, using single-cell RNAseq of bronchoalveolar lavage fluid of nine patients with COVID-19 and three healthy controls, we contribute to both aspects. First, we presented computational supervised machine-learning models with high accuracy in classifying the disease severity (moderate and severe) in patients with COVID-19 starting from single-cell data from bronchoalveolar lavage fluid. Second, we identified regulatory mechanisms from the heterogeneous cell populations in the lungs microenvironment that correlated with different clinical responses. Given the results, patients with moderate COVID-19 symptoms showed an activation/inactivation profile for their analyzed cells leading to a sequential and innocuous immune response. In comparison, severe patients might be promoting cytotoxic and pro-inflammatory responses in a systemic fashion involving epithelial and immune cells without the possibility to develop viral clearance and immune memory. Consequently, we present an in-depth landscape analysis of how transcriptional factors and pathways from these heterogeneous populations can regulate their expression to promote or restrain an effective immune response directly linked to the patients prognosis.

scholarly journals Lung Neutrophilia in Myeloperoxidase Deficient Mice during the Course of Acute Pulmonary Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Silvie Kremserova ◽  
Tomas Perecko ◽  
Karel Soucek ◽  
Anna Klinke ◽  
Stephan Baldus ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Lavage Fluid ◽  
Surface Expression ◽  
Wild Type ◽  
Inflammatory Site ◽  
Chemotactic Factors ◽  
Deficient Mice

Systemic inflammation accompanying diseases such as sepsis affects primarily lungs and induces their failure. This remains the most common cause of sepsis induced mortality. While neutrophils play a key role in pulmonary failure, the mechanisms remain incompletely characterized. We report that myeloperoxidase (MPO), abundant enzyme in neutrophil granules, modulates the course of acute pulmonary inflammatory responses induced by intranasal application of lipopolysaccharide. MPO deficient mice had significantly increased numbers of airway infiltrated neutrophils compared to wild-type mice during the whole course of lung inflammation. This was accompanied by higher levels of RANTES in bronchoalveolar lavage fluid from the MPO deficient mice. Other markers of lung injury and inflammation, which contribute to recruitment of neutrophils into the inflamed lungs, including total protein and other selected proinflammatory cytokines did not significantly differ in bronchoalveolar lavage fluid from the wild-type and the MPO deficient mice. Interestingly, MPO deficient neutrophils revealed a decreased rate of cell death characterized by phosphatidylserine surface expression. Collectively, the importance of MPO in regulation of pulmonary inflammation, independent of its putative microbicidal functions, can be potentially linked to MPO ability to modulate the life span of neutrophils and to affect accumulation of chemotactic factors at the inflammatory site.

scholarly journals Single-cell Transcriptome of Bronchoalveolar Lavage Fluid Reveals Dynamic Change of Macrophages During SARS-CoV-2 Infection in Ferrets

2020 ◽  
Author(s):  
Jeong Seok Lee ◽  
June-Young Koh ◽  
Kijong Yi ◽  
Young-Il Kim ◽  
Su-Jin Park ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Single Cell ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Responses ◽  
Early Stage ◽  
Dynamic Change ◽  
Lavage Fluid ◽  
M2 Macrophages ◽  
Dynamic Features ◽  
Response Dynamics

AbstractAlthough the profile of immune cells changes during the natural course of SARS-CoV-2 inflection in human patients, few studies have used a longitudinal approach to reveal their dynamic features. Here, we performed single-cell RNA sequencing of bronchoalveolar lavage fluid cells longitudinally obtained from SARS-CoV-2-infected ferrets. Landscape analysis of the lung immune microenvironment showed dynamic changes in cell proportions and characteristics in uninfected control, at 2 days post-infection (dpi) (early stage of SARS-CoV-2 infection with peak viral titer), and 5 dpi (resolution phase). NK cells and CD8+ T cells exhibited activated subclusters with interferon-stimulated features, which were peaked at 2 dpi. Intriguingly, macrophages were classified into 10 distinct subpopulations, and their relative proportions changed over the time. We observed prominent transcriptome changes among monocyte-derived infiltrating macrophages and differentiated M1/M2 macrophages, especially at 2 dpi. Moreover, trajectory analysis revealed gene expression changes from monocyte-derived infiltrating macrophages toward M1 or M2 macrophages and identified the distinct macrophage subpopulation that had rapidly undergone SARS-CoV-2-mediated activation of inflammatory responses. Finally, we found that different spectrums of M1 or M2 macrophages showed distinct patterns of gene modules downregulated by immune-modulatory drugs. Overall, these results elucidate fundamental aspects of the immune response dynamics provoked by SARS-CoV-2 infection.

scholarly journals Mechanical Ventilation with Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Pulmonary Inflammation in Patients without Preexisting Lung Injury

2008 ◽  
Vol 108 (1) ◽  
pp. 46-54 ◽  
Author(s):  
Esther K. Wolthuis ◽  
Goda Choi ◽  
Mark C. Dessing ◽  
Paul Bresser ◽  
Rene Lutter ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Responses ◽  
Pulmonary Inflammation ◽  
Lavage Fluid ◽  
Positive End Expiratory Pressure ◽  
Inflammatory Protein ◽  
Macrophage Inflammatory Protein

Background Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury. Methods Patients scheduled to undergo an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes. Results Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P < 0.01). Levels of tumor necrosis factor alpha, IL-1alpha, IL-1beta, IL-6, macrophage inflammatory protein 1alpha, and macrophage inflammatory protein 1beta in the bronchoalveolar lavage fluid were not affected by mechanical ventilation. Plasma levels of IL-6 and IL-8 increased with mechanical ventilation, but there were no differences between the two ventilation groups. Conclusion The use of lower tidal volumes and PEEP may limit pulmonary inflammation in mechanically ventilated patients without preexisting lung injury. The specific contribution of both lower tidal volumes and PEEP on the protective effects of the lung should be further investigated.

scholarly journals Protective Effect of Oxytocin on Ventilator-Induced Lung Injury Through NLRP3-Mediated Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaomei Yang ◽  
Xiaona An ◽  
Cheng Wang ◽  
Feng Gao ◽  
Yicheng Lin ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Protective Effect ◽  
Bronchoalveolar Lavage Fluid ◽  
Life Support ◽  
Inflammatory Responses ◽  
Weight Ratio ◽  
Lavage Fluid ◽  
Caspase 1 ◽  
Ventilator Induced Lung Injury

Mechanical ventilation is an indispensable life-support treatment for acute respiratory failure in critically ill patients, which is generally believed to involve uncontrolled inflammatory responses. Oxytocin (OT) has been reported to be effective in animal models of acute lung injury. However, it is not clear whether Oxytocin has a protective effect on ventilator-induced lung injury (VILI). Therefore, in this study, we aimed to determine whether OT can attenuate VILI and explore the possible mechanism of this protection. To this end, a mouse VILI model was employed. Mice were pretreated with OT 30 min before the intraperitoneal injection of saline or nigericin and ventilation for 4 h, after which they were euthanized. Pathological changes, lung wet/dry (W/D) weight ratio, myeloperoxidase (MPO) activity, the levels of inflammatory cytokines [i.e., interleukin (IL)-1β, IL-6, and IL-18] in lung tissues and bronchoalveolar lavage fluid (BALF), and expression of NLRP3, Toll-like receptor 4 (TLR4), caspase-1, nuclear factor (NF)-κB, and GSDMD in lung tissues were measured. OT treatment could reduce pathological injury, the W/D ratio, and MPO activity in VILI mice. Our data also indicated that OT administration alleviated the expression of TLR4/My-D88 and the activation of NF-κB, NLRP3, and caspase-1 in lung tissues from the VILI mice model. Furthermore, OT also decreased the levels of IL-1β, IL-6, and IL-18 in the bronchoalveolar lavage fluid. Moreover, the OT administration may alleviate the activation of GSDMD partially through its effects on the NLRP3-mediated pathway. Collectively, OT exerted a beneficial effect on VILI by downregulating TLR4-and NLRP3-mediated inflammatory pathways.

Sign in / Sign up

Export Citation Format

Share Document