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Journal of Medical Virology Aug 2023The lung-brain axis is an emerging biological pathway that is being investigated in relation to microbiome medicine. Increasing evidence suggests that pulmonary viral...
The lung-brain axis is an emerging biological pathway that is being investigated in relation to microbiome medicine. Increasing evidence suggests that pulmonary viral infections can lead to distinct pathological imprints in the brain, so there is a need to explore and understand this mechanism and find possible interventions. This study used respiratory syncytial virus (RSV) infection in mice as a model to establish the potential lung-brain axis phenomenon. We hypothesized that RSV infection could disrupt the lung microbiota, compromise immune barriers, and induce a significant shift in microglia phenotype. One week old mice were randomized into the control, Ampicillin, RSV, and RSV+Ampicillin treated groups (n = 6 each). Seven days after the respective treatments, the mice were anaesthetized. Immunofluorescence and real-time qRT-PCR was used to detect virus. Hematoxylin-eosin staining was used to detect histopathology. Malondialdehyde and superoxide dismutase were used to determine oxidative stress and antioxidant capacity. Real-time qRT-PCR and enzyme-linked immunosorbent assay (ELISA) were used to measure Th differentiation in the lung. Real-time qRT-PCR, ELISA, and confocal immunofluorescence were used to determine the microglia phenotype. 16S DNA technology was used to detect lung microflora. RSV infection induces elevated oxidative stress, reduced antioxidant, and significant dysbacteriosis in the lungs of mice. Pulmonary microbes were found to enhance Th1-type immunoreactivity induced by RSV infection and eventually induced M1-type dominant microglia in the brains of mice. This study was able to establish a correlation between the pulmonary microbiome and brain function. Therefore, we recommend a large sample size study with robust data analysis for the long-term effects of antibiotics and RSV infection on brain physiology.
Topics: Mice; Animals; Respiratory Syncytial Virus Infections; Antioxidants; Microglia; Lung; Microbiota; Ampicillin; Mice, Inbred BALB C
PubMed: 37522339
DOI: 10.1002/jmv.28976 -
Current Opinion in Pulmonary Medicine May 2024This review highlights the epidemiology, pathogenesis and clinical management of pulmonary infections caused by emerging fungal organisms. (Review)
Review
PURPOSE OF REVIEW
This review highlights the epidemiology, pathogenesis and clinical management of pulmonary infections caused by emerging fungal organisms.
RECENT FINDINGS
Emerging fungal infections have arisen as a result of population and environmental changes. An enlarging pool of immunocompromised hosts on triazole antifungal prophylaxis has led to an increased incidence of non- Aspergillus molds, such as Fusarium , Scedosporium and Lomentospora spp. Advances in diagnostic capabilities led to the identification of the Emergomyces genus and non- dermatitidis Blastomyces species, which have a significant disease burden in Africa and the Middle East. Climate change has contributed to changing the distribution of previously confined endemic mycoses, like coccidioidomycosis and talaromycosis. These emerging organisms pose important diagnostic and therapeutic challenges.
SUMMARY
Newly recognized pathogenic fungi and established endemic mycoses with expanding geographic boundaries have become important agents of pulmonary disease. There is a dearth of clinical evidence on the appropriate management of these infections.
Topics: Humans; Mycoses; Fungi; Antifungal Agents; Pneumonia; Lung
PubMed: 38411158
DOI: 10.1097/MCP.0000000000001059 -
Zhonghua Jie He He Hu Xi Za Zhi =... May 2024An elderly woman with a 1-year history of pulmonary shadows was admitted because of intermittent cough and sputum production for 2 months. Chest computed tomography (CT)...
An elderly woman with a 1-year history of pulmonary shadows was admitted because of intermittent cough and sputum production for 2 months. Chest computed tomography (CT) scans showed bilateral consolidations and ground-glass opacities, with areas of low attenuation inside consolidative opacities on the mediastinal window. Previous history of radiotherapy for nasopharyngeal carcinoma and long-term use of a compound menthol nasal drops provided were important clues to the diagnosis. CT scan-guided needle lung biopsy and bronchoalveolar lavage were performed, and lipid-laden macrophages were confirmed in both bronchoalveolar lavage and lung tissue. Final diagnosis of exogenous lipoid pneumonia was made on the basis of her risk factors for aspiration, history of oil exposure, and classic radiological and histopathological features. Symptoms improved after discontinuation of causative exposure. It is important for clinicians to raise awareness of exogenous lipoid pneumonia and other aspiration lung diseases.
Topics: Humans; Female; Aged; Pneumonia, Lipid; Tomography, X-Ray Computed; Lung
PubMed: 38706066
DOI: 10.3760/cma.j.cn112147-20231103-00290 -
Clinics in Chest Medicine Dec 2023Patients with nontuberculous mycobacterial (NTM) lung infection require life-long attention to their bronchiectasis, whether or not their NTM infection has been cured.... (Review)
Review
Patients with nontuberculous mycobacterial (NTM) lung infection require life-long attention to their bronchiectasis, whether or not their NTM infection has been cured. The identification of the cause of bronchiectasis and/or coexisting diseases is important because it may affect therapeutic strategies. Airway clearance is the mainstay of bronchiectasis management. It can include multiple breathing techniques, devices, and mucoactive agents. The exact airway clearance regimen should be customized to each individual patient. Chronic pathogenic airway bacteria, such as Pseudomonas aeruginosa, may warrant consideration of eradication therapy and/or chronic use of maintenance inhaled antibiotics.
Topics: Humans; Bronchiectasis; Lung; Mycobacterium Infections, Nontuberculous; Lung Diseases; Nontuberculous Mycobacteria; Anti-Bacterial Agents
PubMed: 37890912
DOI: 10.1016/j.ccm.2023.07.005 -
Frontiers in Immunology 2023Influenza A, the most common subtype, induces 3 to 5 million severe infections and 250,000 to 500,000 deaths each year. Vaccination is traditionally considered to be the... (Review)
Review
Influenza A, the most common subtype, induces 3 to 5 million severe infections and 250,000 to 500,000 deaths each year. Vaccination is traditionally considered to be the best way to prevent influenza A. Yet because the Influenza A virus (IAV) is highly susceptible to antigenic drift and Antigenic shift, and because of the lag in vaccine production, this poses a significant challenge to vaccine effectiveness. Additionally, much information about the resistance of antiviral drugs, such as Oseltamivir and Baloxavir, has been reported. Therefore, the search for alternative therapies in the treatment of influenza is warranted. Recent studies have found that regulating the gut microbiota (GM) can promote the immune effects of anti-IAV via the gut-lung axis. This includes promoting IAV clearance in the early stages of infection and reducing inflammatory damage in the later stages. In this review, we first review the specific alterations in GM observed in human as well as animal models regarding IAV infection. Then we analyzed the effect of GM on host immunity against IAV, including innate immunity and subsequent adaptive immunity. Finally, our study also summarizes the effects of therapies using probiotics, prebiotics, or herbal medicine in influenza A on intestinal microecological composition and their immunomodulatory effects against IAV.
Topics: Animals; Humans; Influenza, Human; Orthomyxoviridae Infections; Gastrointestinal Microbiome; Lung; Influenza A virus
PubMed: 37928517
DOI: 10.3389/fimmu.2023.1147724 -
Proceedings of the National Academy of... Nov 2023COVID-19 pneumonia causes acute lung injury and acute respiratory distress syndrome (ALI/ARDS) characterized by early pulmonary endothelial and epithelial injuries with...
COVID-19 pneumonia causes acute lung injury and acute respiratory distress syndrome (ALI/ARDS) characterized by early pulmonary endothelial and epithelial injuries with altered pulmonary diffusing capacity and obstructive or restrictive physiology. Growth hormone-releasing hormone receptor (GHRH-R) is expressed in the lung and heart. GHRH-R antagonist, MIA-602, has been reported to modulate immune responses to bleomycin lung injury and inflammation in granulomatous sarcoidosis. We hypothesized that MIA-602 would attenuate rVSV-SARS-CoV-2-induced pulmonary dysfunction and heart injury in a BSL-2 mouse model. Male and female K18-htg mice were inoculated with SARS-CoV-2/USA-WA1/2020, BSL-2-compliant recombinant VSV-eGFP-SARS-CoV-2-Spike (rVSV-SARS-CoV-2), or PBS, and lung viral load, weight loss, histopathology, and gene expression were compared. K18-htg mice infected with rVSV-SARS-CoV-2 were treated daily with subcutaneous MIA-602 or vehicle and conscious, unrestrained plethysmography performed on days 0, 3, and 5 (n = 7 to 8). Five days after infection mice were killed, and blood and tissues collected for histopathology and protein/gene expression. Both native SARS-CoV-2 and rVSV-SARS-CoV-2 presented similar patterns of weight loss, infectivity (~60%), and histopathologic changes. Daily treatment with MIA-602 conferred weight recovery, reduced lung perivascular inflammation/pneumonia, and decreased lung/heart ICAM-1 expression compared to vehicle. MIA-602 rescued altered respiratory rate, increased expiratory parameters (Te, PEF, EEP), and normalized airflow parameters (Penh and Rpef) compared to vehicle, consistent with decreased airway inflammation. RNASeq followed by protein analysis revealed heightened levels of inflammation and end-stage necroptosis markers, including ZBP1 and pMLKL induced by rVSV-SARS-CoV-2, that were normalized by MIA-602 treatment, consistent with an anti-inflammatory and pro-survival mechanism of action in this preclinical model of COVID-19 pneumonia.
Topics: Mice; Male; Female; Animals; SARS-CoV-2; COVID-19; Lung; Inflammation; Respiratory Distress Syndrome; Weight Loss; Mice, Transgenic; Disease Models, Animal
PubMed: 37983492
DOI: 10.1073/pnas.2308342120 -
International Journal of Molecular... Apr 2024Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of... (Review)
Review
Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID.
Topics: Humans; COVID-19; SARS-CoV-2; Lung; Pulmonary Embolism; Hypertension, Pulmonary; Post-Acute COVID-19 Syndrome; Thrombosis
PubMed: 38732160
DOI: 10.3390/ijms25094941 -
Microbiology Spectrum Aug 2023Invasive aspergillosis is initiated when Aspergillus fumigatus adheres to and invades the pulmonary epithelial cells that line the airways and alveoli. To gain deeper...
Invasive aspergillosis is initiated when Aspergillus fumigatus adheres to and invades the pulmonary epithelial cells that line the airways and alveoli. To gain deeper insight into how pulmonary epithelial cells respond to A. fumigatus invasion, we used transcriptome sequencing (RNA-seq) to determine the transcriptional response of the A549 type II alveolar epithelial cell line to infection with strains CEA10 and Af293, two clinical isolates of A. fumigatus. Upstream regulator analysis of the data indicated that while both strains activated virtually identical host cell signaling pathways after 16 h of infection, only strain CEA10 activated these pathways after 6 h of infection. Many of the pathways that were predicted to be activated by A. fumigatus, including the tumor necrosis factor (TNF), interleukin-1α (IL-1α), IL-1β, IL-17A, Toll-like receptor 2 (TLR2), and TLR4 pathways, are known to be critical for the host defense against this fungus. We also found that the platelet-derived growth factor BB (PDGF BB) and progesterone receptor (PGR) pathways were activated by A. fumigatus. Using pharmacologic inhibitors, we determined that blocking the PDGF receptor or PGR inhibited the endocytosis of both strains of A. fumigatus in an additive manner. Both the PDGF BB and PGR pathways are also predicted to be activated by infection of A549 cells with other molds, such as Rhizopus delemar and Rhizopus oryzae. Thus, these pathways may represent a common response of pulmonary epithelial cells to mold infection. Invasive aspergillosis is a deadly invasive fungal infection that initiates when Aspergillus fumigatus spores are inhaled and come into contact with the epithelial cells that line the airways and alveoli. Understanding this fungus-host interaction is important for the development of novel therapeutics. To gain a deeper understanding of how these airway epithelial cells respond to A. fumigatus during infection, we used RNA-seq to determine the transcriptional response of alveolar epithelial cells to infection with two different clinical isolates of A. fumigatus. Our analysis identified new host response pathways that have not previously been tied to infection with A. fumigatus. Pharmacological inhibition of two of these pathways inhibited the ability of A. fumigatus to invade airway epithelial cells. These two pathways are also predicted to be activated by infection with other filamentous fungi. Thus, these pathways may represent a common response of alveolar epithelial cells to mold infection.
Topics: Humans; Aspergillus fumigatus; Becaplermin; Aspergillosis; Epithelial Cells; Lung
PubMed: 37255456
DOI: 10.1128/spectrum.00084-23 -
Frontiers in Cellular and Infection... 2023Pneumoconiosis patients have a high prevalence of pulmonary infections, which can complicate diagnosis and treatment. And there is no comprehensive study of the...
BACKGROUND
Pneumoconiosis patients have a high prevalence of pulmonary infections, which can complicate diagnosis and treatment. And there is no comprehensive study of the microbiome of patients with pneumoconiosis. The application of metagenomic next-generation sequencing (mNGS) fills the gap to some extent by analyzing the lung microbiota of pneumoconiosis population while achieving accurate diagnosis.
METHODS
We retrospectively analyzed 44 patients with suspected pneumoconiosis complicated with pulmonary infection between Jan 2020 and Nov 2022. Bronchoalveolar lavage fluid (BALF) specimens from 44 patients were collected and tested using the mNGS technology.
RESULTS
Among the lung microbiome of pneumoconiosis patients with complicated pulmonary infection (P group), the most frequently detected bacteria and fungi at the genus level were and , at the species level were and , respectively, and the most frequently detected DNA virus was . There was no significant difference in α diversity between the P group and the non-pneumoconiosis patients complicated with pulmonary infection group (Non-P group) in pulmonary flora, while 0.01 for β diversity analysis, and the differential species between the two groups were and . In addition, we monitored a high distribution of and in the P group, while herpes virus was detected in the majority of samples.
CONCLUSIONS
Overall, we not only revealed a comprehensive lung microbiome profile of pneumoconiosis patients, but also compared the differences between their microbiome and that of non-pneumoconiosis complicated with pulmonary infection patients. This provides a good basis for a better understanding of the relationship between pneumoconiosis and microorganisms, and for the search of potential biomarkers.
Topics: Humans; Retrospective Studies; Pneumonia; Microbiota; High-Throughput Nucleotide Sequencing; Biomarkers; Lung; Sensitivity and Specificity; Metagenomics
PubMed: 37545858
DOI: 10.3389/fcimb.2023.1200157 -
American Journal of Physiology. Lung... May 2024Acute respiratory distress syndrome (ARDS) is a fatal pulmonary disorder characterized by severe hypoxia and inflammation. ARDS is commonly triggered by systemic and... (Review)
Review
Acute respiratory distress syndrome (ARDS) is a fatal pulmonary disorder characterized by severe hypoxia and inflammation. ARDS is commonly triggered by systemic and pulmonary infections, with bacteria and viruses. Notable pathogens include , , , coronaviruses, influenza viruses, and herpesviruses. COVID-19 ARDS represents the latest etiological phenotype of the disease. The pathogenesis of ARDS caused by bacteria and viruses exhibits variations in host immune responses and lung mesenchymal injury. We postulate that the systemic and pulmonary metabolomics profiles of ARDS induced by COVID-19 pathogens may exhibit distinctions compared with those induced by other infectious agents. This review aims to compare metabolic signatures in blood and lung specimens specifically within the context of ARDS. Both prevalent and phenotype-specific metabolomic signatures, including but not limited to glycolysis, ketone body production, lipid oxidation, and dysregulation of the kynurenine pathways, were thoroughly examined in this review. The distinctions in metabolic signatures between COVID-19 and non-COVID ARDS have the potential to reveal new biomarkers, elucidate pathogenic mechanisms, identify druggable targets, and facilitate differential diagnosis in the future.
Topics: Humans; COVID-19; Respiratory Distress Syndrome; SARS-CoV-2; Lung; Metabolome; Biomarkers; Metabolomics
PubMed: 38469648
DOI: 10.1152/ajplung.00266.2023