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Frontiers in Cellular and Infection... 2011Burkholderia cenocepacia is an opportunistic respiratory pathogen of individuals with cystic fibrosis (CF). Some strains of B. cenocepacia are highly transmissible and... (Review)
Review
Burkholderia cenocepacia is an opportunistic respiratory pathogen of individuals with cystic fibrosis (CF). Some strains of B. cenocepacia are highly transmissible and resistant to almost all antibiotics. Approximately one-third of B. cenocepacia infected CF patients go on to develop fatal "cepacia syndrome." During the last two decades, substantial progress has been made with regards to evasion of host innate defense mechanisms by B. cenocepacia. Almost all strains of B. cenocepacia have the capacity to survive and replicate intracellularly in both airway epithelial cells and macrophages, which are primary sentinels of the lung and play a pivotal role in clearance of infecting bacteria. Those strains of B. cenocepacia, which express both cable pili and the associated 22 kDa adhesin are also capable of transmigrating across airway epithelium and persist in mouse models of infection. In this review, we will discuss how this type of interaction between B. cenocepacia and host may lead to persistence of bacteria as well as lung inflammation in CF patients.
Topics: Animals; Burkholderia Infections; Burkholderia cenocepacia; Cystic Fibrosis; Cytokines; Disease Models, Animal; Endocytosis; Host-Pathogen Interactions; Humans; Immunity, Innate; Inflammation Mediators; Lung; Mice; Opportunistic Infections; Respiratory Mucosa; Respiratory Tract Infections; Toll-Like Receptors
PubMed: 22919590
DOI: 10.3389/fcimb.2011.00025 -
Infection and Immunity Mar 2018Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel...
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with , which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with We established a new mouse model to investigate the relationship between and pulmonary infections. In this model, animals exposed to and coinfected with exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with alone. This increased control of infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in control in -coinfected lungs. Our results demonstrate that , an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact control in a mouse model.
Topics: Animals; Aspergillosis; Aspergillus fumigatus; Coinfection; Cystic Fibrosis; Female; Humans; Interleukin-17; Lung; Male; Mice; Mice, Inbred C57BL; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus
PubMed: 29263106
DOI: 10.1128/IAI.00859-17 -
International Journal of Chronic... 2012Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory condition in adults and is characterized by progressive airflow limitation that is... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is the most common chronic respiratory condition in adults and is characterized by progressive airflow limitation that is not fully reversible. The main etiological agents linked with COPD are cigarette smoking and biomass exposure but respiratory infection is believed to play a major role in the pathogenesis of both stable COPD and in acute exacerbations. Acute exacerbations are associated with more rapid decline in lung function and impaired quality of life and are the major causes of morbidity and mortality in COPD. Preventing exacerbations is a major therapeutic goal but currently available treatments for exacerbations are not very effective. Historically, bacteria were considered the main infective cause of exacerbations but with the development of new diagnostic techniques, respiratory viruses are also frequently detected in COPD exacerbations. This article aims to provide a state-of-the art review of current knowledge regarding the role of infection in COPD, highlight the areas of ongoing debate and controversy, and outline emerging technologies and therapies that will influence future diagnostic and therapeutic pathways in COPD.
Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Disease Progression; Humans; Lung; Prognosis; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Risk Assessment; Risk Factors; Smoking
PubMed: 22969296
DOI: 10.2147/COPD.S28286 -
The American Journal of Pathology Feb 2021The severe acute respiratory syndrome coronavirus 2 pandemic has infected millions of individuals in the United States and caused hundreds of thousands of deaths. Direct... (Review)
Review
The severe acute respiratory syndrome coronavirus 2 pandemic has infected millions of individuals in the United States and caused hundreds of thousands of deaths. Direct infection of extrapulmonary tissues has been postulated, and using sensitive techniques, viral RNA has been detected in multiple organs in the body, including the kidney. However, direct infection of tissues outside of the lung has been more challenging to demonstrate. This has been in part due to misinterpretation of electron microscopy studies. In this perspective, we will discuss what is known about coronavirus infection, some of the basic ultrastructural cell biology that has been confused for coronavirus infection of cells, and rigorous criteria that should be used when identifying pathogens by electron microscopy.
Topics: COVID-19; Coronavirus Infections; Humans; Lung; Microscopy, Electron; SARS-CoV-2; United States; Virus Diseases
PubMed: 33227297
DOI: 10.1016/j.ajpath.2020.11.003 -
Retrovirology Jan 2021The lung is one of several organs that can be affected by HTLV-1 mediated inflammation. Pulmonary inflammation associated with HTLV-1 infection involves the... (Review)
Review
The lung is one of several organs that can be affected by HTLV-1 mediated inflammation. Pulmonary inflammation associated with HTLV-1 infection involves the interstitium, airways and alveoli, resulting in several clinical entities including interstitial pneumonias, bronchiolitis and alveolitis, depending on which structures are most affected. Augmentation of the inflammatory effects of HTLV-1 infected lymphocytes by recruitment of other inflammatory cells in a positive feedback loop is likely to underlie the pathogenesis of HTLV-1 associated pulmonary disease, as has been proposed for HTLV-1 associated myelopathy. In contrast to the conclusions of early case series, HTLV-1 associated pulmonary disease can be associated with significant parenchymal damage, which may progress to bronchiectasis where this involves the airways. Based on our current understanding of HTLV-1 associated pulmonary disease, diagnostic criteria are proposed.
Topics: Animals; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Inflammation; Lung; Lung Diseases; Mice; Paraparesis, Tropical Spastic
PubMed: 33407607
DOI: 10.1186/s12977-020-00543-z -
Journal of Microbiology and... Aug 2021is a type of pathogenic gram-negative bacteria that causes various respiratory tract infections including asthma. species infect humans and cause respiratory infection...
is a type of pathogenic gram-negative bacteria that causes various respiratory tract infections including asthma. species infect humans and cause respiratory infection by rupturing the lining of the respiratory which includes the throat, lungs and windpipe. Meanwhile, the function of interleukin-4 (IL-4) in respiratory infection and its association with the development of airway hyperresponsiveness (AHR) in adulthood and causing allergic airway disease (AAD) are not understood properly. We therefore investigated the role of IL-4 in respiratory infection and allergy caused by early life infection. In this study, Ch. pneumonia strain was propagated and cultured in HEp-2 cells according to standard protocol and infant C57BL/6 mice around 3-4 weeks old were infected to study the role of IL-4 in respiratory infection and allergy caused by early life infection. We observed that IL-4 is linked with respiratory infection and its absence lowers respiratory infection. IL-4R α2 is also responsible for controlling the IL-4 signaling pathway and averts the progression of infection and inflammation. Furthermore, the IL-4 signaling pathway also influences infection-induced AHR and aids in increasing AAD severity. STAT6 also promotes respiratory infection caused by and further enhanced its downstream process. Our study concluded that IL-4 is a potential target for preventing infection-induced AHR and severe asthma.
Topics: Animals; Chlamydia Infections; Chlamydophila pneumoniae; Interleukin-4; Lung; Macrophage Activation; Mice; Mice, Inbred C57BL; Receptors, Cell Surface; Respiratory Hypersensitivity; Respiratory Tract Infections; Signal Transduction
PubMed: 34226412
DOI: 10.4014/jmb.2104.04028 -
European Respiratory Review : An... Sep 2013Idiopathic pulmonary fibrosis (IPF) is a progressive, and invariably fatal, condition that is believed to arise in genetically susceptible individuals as a consequence... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a progressive, and invariably fatal, condition that is believed to arise in genetically susceptible individuals as a consequence of an aberrant wound-healing response following repetitive alveolar injury. The exact triggers, which initiate the fibrotic process, remain unknown. Infectious agents, including both viruses and bacteria, have the capacity to cause alveolar-epithelial cell injury and apoptosis. Relatively few studies have examined the role of infection in IPF. Those that have, point to viruses playing a key role as cofactors in the initiation and progression of IPF. There is also some evidence to suggest that viral infection may be responsible for a proportion of acute exacerbations of IPF. The role played by bacteria in the pathogenesis of IPF is less clear cut. Studies from other respiratory diseases suggest that alterations in the lung microbiome are associated with disease and that these changes influence disease behaviour. Emerging molecular microbiological techniques are making the study of microbial communities in the lung easier. It is hoped that by combining such techniques with the careful longitudinal phenotyping of patients with IPF, it will be possible to elucidate the role played by bacteria and viruses in the pathogenesis of the disease. If infection plays a causal role in IPF then it is possible that therapeutic strategies, utilising currently available antiviral or antibiotic drugs, may be effective in modifying the course of this devastating condition.
Topics: Animals; Anti-Bacterial Agents; Antiviral Agents; Bacterial Infections; Humans; Idiopathic Pulmonary Fibrosis; Lung; Respiratory Tract Infections; Risk Factors; Treatment Outcome; Virus Diseases
PubMed: 23997064
DOI: 10.1183/09059180.00000713 -
Cell Reports Feb 2019Lung interstitial CD4+ T cells are critical for protection against pulmonary infections, but the fate of this population during HIV-1 infection is not well described....
Lung interstitial CD4+ T cells are critical for protection against pulmonary infections, but the fate of this population during HIV-1 infection is not well described. We studied CD4+ T cells in the setting of HIV-1 infection in human lung tissue, humanized mice, and a Mycobacterium tuberculosis (Mtb)/simian immunodeficiency virus (SIV) nonhuman primate co-infection model. Infection with a CCR5-tropic strain of HIV-1 or SIV results in severe and rapid loss of lung interstitial CD4+ T cells but not blood or lung alveolar CD4+ T cells. This is accompanied by high HIV-1 production in these cells in vitro and in vivo. Importantly, during early SIV infection, loss of lung interstitial CD4+ T cells is associated with increased dissemination of pulmonary Mtb infection. We show that lung interstitial CD4+ T cells serve as an efficient target for HIV-1 and SIV infection that leads to their early depletion and an increased risk of disseminated tuberculosis.
Topics: Animals; CD4-Positive T-Lymphocytes; Coinfection; Female; HEK293 Cells; HIV Infections; HIV-1; Humans; Lung; Macaca mulatta; Mice; Mycobacterium tuberculosis; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Tuberculosis, Pulmonary
PubMed: 30726727
DOI: 10.1016/j.celrep.2019.01.021 -
Biomedicine & Pharmacotherapy =... Nov 2021Trillions of beneficial and hostile microorganisms live in the human respiratory and gastrointestinal tracts, which act as gatekeepers in maintaining human health, i.e.,... (Review)
Review
Trillions of beneficial and hostile microorganisms live in the human respiratory and gastrointestinal tracts, which act as gatekeepers in maintaining human health, i.e., protecting the body from pathogens by colonizing mucosal surfaces with microbiota-derived antimicrobial metabolites such as short-chain fatty acids or host-derived cytokines and chemokines. It is widely accepted that the microbiome interacts with each other and with the host in a mutually beneficial relationship. Microbiota in the respiratory tract may also play a crucial role in immune homeostasis, maturation, and maintenance of respiratory physiology. Anti-TB antibiotics may cause dysbiosis in the lung and intestinal microbiota, affecting colonization resistance and making the host more susceptible to Mycobacterium tuberculosis (M. tuberculosis) infection. This review discusses recent advances in our understanding of the lung microbiota composition, the lungs and intestinal microbiota related to respiratory health and diseases, microbiome sequencing and analysis, the bloodstream, and the lymphatic system that underpin the gut-lung axis in M. tuberculosis-infected humans and animals. We also discuss the gut-lung axis interactions with the immune system, the role of the microbiome in TB pathogenesis, and the impact of anti-TB antibiotic therapy on the microbiota in animals, humans, and drug-resistant TB individuals.
Topics: Animals; Antitubercular Agents; Dysbiosis; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Lung; Metagenome; Mycobacterium tuberculosis; Tuberculosis, Pulmonary
PubMed: 34560539
DOI: 10.1016/j.biopha.2021.112108 -
Respiratory Research Dec 2004Coccidioidomycosis or Valley Fever is caused by Coccidioides in Southwest US and Central America. Primary pulmonary infection is initiated by inhalation of air-borne...
BACKGROUND
Coccidioidomycosis or Valley Fever is caused by Coccidioides in Southwest US and Central America. Primary pulmonary infection is initiated by inhalation of air-borne arthroconidia. Since, lung is the first organ that encounters arthroconidia, different components of the pulmonary innate immune system may be involved in the regulation of host defense. Pulmonary surfactant proteins (SP)-A and SP-D have been recognized to play an important role in binding and phagocytosis of various microorganisms, but their roles in Coccidioides infection are not known.
METHODS
In this study, we studied the changes in amounts of pulmonary SP-A, SP-D and phospholipid in murine model of Coccidioides posadasii infection, and binding of SP-A and SP-D to Coccidioidal antigens. Mice were challenged intranasally with a lethal dose of C. posadasii (n = 30 arthroconidia) and bronchoalveolar lavage fluid (BALF) samples were collected on day 10, post infection. In another group of animals, mice were immunized with protective formalin killed spherule (FKS) vaccine prior to infection. The concentrations of BALF SP-A, SP-D, total phospholipid were measured using enzyme linked immunosorbent assay and biochemical assays.
RESULTS
We found that in lavage fluid samples of C. posadasii infected mice, the concentrations of total phospholipid, SP-A and SP-D were 17 % (SEM 3.5, p < 0.001), 38 % (SEM 5.8, p < 0.001) and 4 % (SEM 1.3, p < 0.001) of those in lavage fluid samples of non-infected control mice, respectively. However, the concentrations of SP-A and SP-D remained unchanged in BALF samples of C. posadasii protected mice after immunization with FKS vaccine. Also, we found that both SP-A and SP-D bind to Coccidiodal antigens.
CONCLUSION
Our results suggest that the C. posadasii infection perturbs the pulmonary SP-A, SP-D, and phospholipids, potentially enabling the disease progression and promoting fungal dissemination.
Topics: Adaptation, Physiological; Animals; Bronchoalveolar Lavage Fluid; Coccidioides; Coccidioidomycosis; Female; Lung; Lung Diseases, Fungal; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Protein D
PubMed: 15588319
DOI: 10.1186/1465-9921-5-28