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International Journal of Chronic... 2014Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute... (Review)
Review
Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations. The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract. The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations. In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD. In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes. This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans.
Topics: Adaptive Immunity; Animals; Haemophilus Infections; Haemophilus Vaccines; Haemophilus influenzae; Host-Pathogen Interactions; Humans; Immunity, Innate; Lung; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections
PubMed: 25342897
DOI: 10.2147/COPD.S54477 -
Frontiers in Cellular and Infection... 2019Programmed cell death and especially necroptosis, a programmed and regulated form of necrosis, have been recently implicated in the progression and outcomes of influenza...
Programmed cell death and especially necroptosis, a programmed and regulated form of necrosis, have been recently implicated in the progression and outcomes of influenza in mouse models. Moreover, Z-DNA/RNA binding protein 1 (ZBP1) has been identified as a key signaling molecule for necroptosis induced by Influenza A virus (IAV). Direct evidence of IAV-induced necroptosis has not been shown in infected lungs . It is also unclear as to what cell types undergo necroptosis during pulmonary IAV infection and whether ZBP1 expression can be regulated by inflammatory mediators. In this study, we found that IAV infection induced ZBP1 expression in mouse lungs. We identified that mediators implicated in the pathogenesis of IAV infection including interferons (IFNs), TNFα, and agonists for Toll-like receptors 3 and 4 were potent inducers of ZBP1 expression in primary murine alveolar epithelial cells, bone marrow derived macrophages, and dendritic cells. We further found that IAV infection induced a strong necroptosis through phosphorylation of the necroptosis effector mixed lineage kinase domain-like protein in infiltrating immune cells and alveolar epithelial cells by day 7 post-infection. Lastly, we found different cell type-specific responses to IAV-induced cell death upon inhibition of caspases and/or necroptosis pathways. Our findings provide direct evidence that IAV infection induces necroptosis in mouse lungs, which may involve local induction of ZBP1 and different programmed cell death signaling mechanisms in alveolar epithelial and infiltrating inflammatory cells in the lungs.
Topics: Alveolar Epithelial Cells; Animals; Biomarkers; Cytokines; Gene Expression; Host-Pathogen Interactions; Immunohistochemistry; Inflammation Mediators; Influenza A virus; Lung; Mice; Necroptosis; Orthomyxoviridae Infections; Phosphorylation; RNA-Binding Proteins
PubMed: 31440477
DOI: 10.3389/fcimb.2019.00286 -
Journal of Microbiology, Immunology,... Dec 2021Toxocara canis, a source of visceral larva migrans, causes toxocariasis and induces respiratory symptoms. The reasons by which the pulmonary pathological alteration in...
BACKGROUND
Toxocara canis, a source of visceral larva migrans, causes toxocariasis and induces respiratory symptoms. The reasons by which the pulmonary pathological alteration in the lungs infected with T. canis remain unclear.
METHODS
The involvement of the pulmonary pathological alteration by histology, enzyme activity, and Western blot analysis in the lungs of BALB/c mice after the infection of 2000 embryonated eggs.
RESULTS
The pathological effects gradually increased after the infection culminated in severe leukocyte infiltration and hemorrhage from days 4-14 post-inoculation. Gelatin zymography using substrate showed that the relative activity of matrix metalloproteinase (MMP) -9 and MMP-2 significantly increased in T. canis-infected mice. Western blot analysis indicated that the MMPs protein level of fibronectin monomer significantly increased in T. canis-infected mice compared with that in uninfected control. T. canis larvae mainly initiated leukocyte infiltration and hemorrhage in the lungs.
CONCLUSION
These phenomena subsequently induced the activities of MMPs in parallel with the pathological changes in early stage pulmonary inflammation. In conclusion, T. canis larval migration activated the MMPs and caused pulmonary pathogenesis.
Topics: Animals; Fibronectins; Hemorrhage; Larva; Leukocytes; Lung; Male; Matrix Metalloproteinases; Mice; Mice, Inbred BALB C; Toxocara canis; Toxocariasis
PubMed: 32826193
DOI: 10.1016/j.jmii.2020.07.022 -
Pathology, Research and Practice Nov 2020During the COVID-19 pandemic, many deaths occurred especially among the old patients with cardiovascular comorbidities. Many questions have been asked and few simple... (Review)
Review
During the COVID-19 pandemic, many deaths occurred especially among the old patients with cardiovascular comorbidities. Many questions have been asked and few simple answers have been given. The autopsy data are few and the aspects often observed are pulmonary diffuse alveolar damage (DAD), myocarditis, acute myocardial infarction (AMI), and disseminated intravascular coagulation (DIC); these aspects are not only in COVID-19 but also in other viral infections and in sepsis. It should be considered that coronavirus with its pathological organ changes have already been described in the years preceding the pandemic.
Topics: Autopsy; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Lung; Myocarditis; Pandemics; Pathologists; Pneumonia, Viral; SARS-CoV-2
PubMed: 32890939
DOI: 10.1016/j.prp.2020.153195 -
European Respiratory Review : An... Mar 2019Chronic obstructive pulmonary disease (COPD) is currently the third most common cause of global mortality. Acute exacerbations of COPD frequently necessitate hospital... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is currently the third most common cause of global mortality. Acute exacerbations of COPD frequently necessitate hospital admission to enable more intensive therapy, incurring significant healthcare costs. COPD exacerbations are also associated with accelerated lung function decline and increased risk of mortality. Until recently, bacterial pathogens were believed to be responsible for the majority of disease exacerbations. However, with the advent of culture-independent molecular diagnostic techniques it is now estimated that viruses are detected during half of all COPD exacerbations and are associated with poorer clinical outcomes. Human rhinovirus, respiratory syncytial virus and influenza are the most commonly detected viruses during exacerbation. The role of persistent viral infection (adenovirus) has also been postulated as a potential pathogenic mechanism in COPD. Viral pathogens may play an important role in driving COPD progression by acting as triggers for exacerbation and subsequent lung function decline whilst the role of chronic viral infection remains a plausible hypothesis that requires further evaluation. There are currently no effective antiviral strategies for patients with COPD. Herein, we focus on the current understanding of the cellular and molecular mechanisms of respiratory viral infection in COPD.
Topics: Host-Pathogen Interactions; Humans; Lung; Prognosis; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Risk Factors; Virulence; Virus Diseases; Viruses
PubMed: 30872396
DOI: 10.1183/16000617.0063-2018 -
Tuberculosis (Edinburgh, Scotland) Jan 2021Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are currently the two main causes of death among infectious diseases. There is an increasing number of studies...
Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are currently the two main causes of death among infectious diseases. There is an increasing number of studies trying to elucidate the interactions between Mycobacterium tuberculosis and SARS-CoV-2. Some of the first case reports point to a worsening of respiratory symptoms in co-infected TB/COVID-19 individuals. However, data from the cohort studies has shown some conflicting results. This study proposes to conduct a systematic review on the current literature on TB/COVID-19 co-infection cohorts, evaluating clinical and epidemiological data, focusing on its implications to the immune system. From an immunological perspective, the TB/COVID-19 co-infection has the potential to converge in a "perfect storm". The disorders induced by each pathogen to the immunomodulation tend to induce an unbalanced inflammatory response, which can promote the progression and worsening of both diseases. Understanding the nature of the interactions between M. tuberculosis and SARS-CoV-2 will be crucial for the development of therapeutic strategies against co-infection.
Topics: Animals; COVID-19; Coinfection; Disease Progression; Host-Pathogen Interactions; Humans; Inflammation Mediators; Lung; Mycobacterium tuberculosis; Prognosis; SARS-CoV-2; Signal Transduction; Tuberculosis, Pulmonary
PubMed: 33246269
DOI: 10.1016/j.tube.2020.102020 -
Inflammopharmacology Feb 2020Influenza is an acute viral respiratory illness that causes high morbidity and mortality globally. Therapeutic actions are limited to vaccines and a few anti-viral...
BACKGROUND
Influenza is an acute viral respiratory illness that causes high morbidity and mortality globally. Therapeutic actions are limited to vaccines and a few anti-viral drugs. Polygala (P.) japonica herba is rich in Polygalasaponin F (PSF, CHO), used for acute bronchitis, pharyngitis, pneumonia, amygdalitis, and respiratory tract infections treatment in China. Hypercytokinemia is often correlated with severe pneumonia caused by several influenza viruses. PSF was reported to have anti-inflammatory effects and its mechanism is associated with the nuclear factor (NF)-κB signaling pathway. The action of PSF to alleviate pulmonary inflammation caused by influenza A virus (IAV) infection requires careful assessment. In the present study, we evaluated the effect and mechanism of PSF on mice with pneumonia caused by influenza H1N1 (A/FM/1/47).
METHODS
Mice were infected intranasally with fifteen 50% mouse lethal challenge doses (MLD) of influenza virus. BALB/c mice were treated with PSF or oseltamivir (oral administration) for 2 h post-infection and received concomitant treatment for 5 days after infection. On day 6 post-infection, 10 mice per group were killed to collect related samples, measure body weight and lung wet weight, and detect the viral load, cytokine, prostaglandins, pathological changes, and cell pathway protein expression in the lungs. In addition, the survival experiments were carried out to investigate the survival of mice. The expression profile of cell pathway proteins was detected and analyzed using a broad pathway antibody array and confirmed the findings from the array by western blotting.
RESULTS
Polygalasaponin F and oseltamivir can protect against influenza viral infection in mice. PSF and oseltamivir significantly relieved the signs and symptoms, reduced body weight loss, and improved the survival rate of H1N1-infected mice. Moreover, PSF efficiently decreased the level of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, interferon (IFN)-γ, thromboxane A (TXA), and prostaglandin E (PGE) in lung tissues of mice infected with influenza virus (p < 0.05-0.01). Oseltamivir had a similar effect to lung cytokine of PSF, but did not decrease the levels of TXA and PGE. There was a twofold or greater increase in four cell pathway protein, namely NF-κB p65 (2.68-fold), I-kappa-B-alpha (IκBα) (2.56-fold), and MAPK/ERK kinase 1 (MEK1) (7.15-fold) assessed in the array induced by influenza virus. Western blotting showed that the expression of these proteins was significantly decreased in lung after influenza virus challenge in PSF and oseltamivir-treated mice (p < 0.05-0.01).
CONCLUSION
Polygalasaponin F appears to be able to augment protection against IAV infection in mice via attenuation of pulmonary inflammatory responses. Its effect on IAV-induced pulmonary inflammation was associated with suppression of Raf/MEK/ERK and NF-κB expressions.
Topics: Animals; Cytokines; Female; Influenza A Virus, H1N1 Subtype; Lung; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Pneumonia; Saponins; Signal Transduction; Triterpenes
PubMed: 31446589
DOI: 10.1007/s10787-019-00633-1 -
Journal of Leukocyte Biology Nov 2009Viruses that infect the lung are a significant cause of morbidity and mortality in animals and humans worldwide. Coronaviruses are being associated increasingly with... (Review)
Review
Viruses that infect the lung are a significant cause of morbidity and mortality in animals and humans worldwide. Coronaviruses are being associated increasingly with severe diseases in the lower respiratory tract. Alveolar epithelial cells are an important target for coronavirus infection in the lung, and infected cells can initiate innate immune responses to viral infection. In this overview, we describe in vitro models of highly differentiated alveolar epithelial cells that are currently being used to study the innate immune response to coronavirus infection. We have shown that rat coronavirus infection of rat alveolar type I epithelial cells in vitro induces expression of CXC chemokines, which may recruit and activate neutrophils. Although neutrophils are recruited early in infection in several coronavirus models including rat coronavirus. However, their role in viral clearance and/or immune-mediated tissue damage is not understood. Primary cultures of differentiated alveolar epithelial cells will be useful for identifying the interactions between coronaviruses and alveolar epithelial cells that influence the innate immune responses to infection in the lung. Understanding the molecular details of these interactions will be critical for the design of effective strategies to prevent and treat coronavirus infections in the lung.
Topics: Animals; Cell Differentiation; Chemokines, CXC; Coronavirus; Coronavirus Infections; Epithelial Cells; Host-Pathogen Interactions; Humans; Lung; Lung Diseases; Pulmonary Alveoli; Rats; Respiratory Tract Infections; Severe acute respiratory syndrome-related coronavirus; Severe Acute Respiratory Syndrome; Virus Diseases
PubMed: 19638499
DOI: 10.1189/jlb.0209078 -
Scientific Reports Feb 2016Co-infection with HIV increases the morbidity and mortality associated with tuberculosis due to multiple factors including a poorly understood microbial synergy. We...
Co-infection with HIV increases the morbidity and mortality associated with tuberculosis due to multiple factors including a poorly understood microbial synergy. We developed a novel small animal model of co-infection in the humanized mouse to investigate how HIV infection disrupts pulmonary containment of Mtb. Following dual infection, HIV-infected cells were localized to sites of Mtb-driven inflammation and mycobacterial replication in the lung. Consistent with disease in human subjects, we observed increased mycobacterial burden, loss of granuloma structure, and increased progression of TB disease, due to HIV co-infection. Importantly, we observed an HIV-dependent pro-inflammatory cytokine signature (IL-1β, IL-6, TNFα, and IL-8), neutrophil accumulation, and greater lung pathology in the Mtb-co-infected lung. These results suggest that in the early stages of acute co-infection in the humanized mouse, infection with HIV exacerbates the pro-inflammatory response to pulmonary Mtb, leading to poorly formed granulomas, more severe lung pathology, and increased mycobacterial burden and dissemination.
Topics: Animals; Coinfection; Disease Models, Animal; HIV Infections; HIV-1; Immunocompromised Host; Lung; Mice; Neutrophil Infiltration; Tuberculosis, Pulmonary
PubMed: 26908312
DOI: 10.1038/srep21522 -
Nature Communications Nov 2014Copper homeostasis is important for virulence of the fungus Cryptococcus neoformans, which can cause lethal meningoencephalitis in humans. Cryptococcus cells encounter...
Copper homeostasis is important for virulence of the fungus Cryptococcus neoformans, which can cause lethal meningoencephalitis in humans. Cryptococcus cells encounter high copper levels in the lung, where infection is initiated, and low copper levels in the brain. Here we demonstrate that two Cryptococcus copper transporters, Ctr1 and Ctr4, differentially influence fungal survival during pulmonary infection and the onset of meningoencephalitis. Protein Ctr1 is rapidly degraded under the high-copper conditions found in infected lungs, and its loss has no effect in fungal virulence in mice. By contrast, deleting CTR4 results in a hypervirulent phenotype. Overexpressing either Ctr1 or Ctr4 leads to profound reductions in fungal burden in the lung. However, during the onset of meningoencephalitis, expression of the copper transporters is induced and is critical for Cryptococcus virulence. Our work demonstrates that the fungal cells switch between copper detoxification and acquisition to address different copper stresses in the host.
Topics: Animals; Brain; Cation Transport Proteins; Copper; Cryptococcosis; Cryptococcus neoformans; Female; Homeostasis; Ion Transport; Lung; Meningoencephalitis; Mice; Mice, Inbred A; Mice, Inbred C57BL
PubMed: 25417972
DOI: 10.1038/ncomms6550