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Scientific Reports Oct 2019Intestinal helminth infections elicit Th2-type immunity, which influences host immune responses to additional threats, such as allergens, metabolic disease, and other...
Intestinal helminth infections elicit Th2-type immunity, which influences host immune responses to additional threats, such as allergens, metabolic disease, and other pathogens. Th2 immunity involves a shift of the CD4 T-cell population from type-0 to type-2 (Th2) with increased abundance of interleukin (IL)-4 and IL-13. This study sought to investigate if existing gut-restricted intestinal helminth infections impact bacterial-induced acute airway neutrophil recruitment. C57BL/6 mice were divided into four groups: uninfected; helminth-Heligmosomoides polygyrus infected; Pseudomonas aeruginosa infected; and coinfected. Mice infected with H. polygyrus were incubated for 2 weeks, followed by P. aeruginosa intranasal inoculation. Bronchial alveolar lavage, blood, and lung samples were analyzed. Interestingly, infection with gut-restricted helminths resulted in immunological and structural changes in the lung. These changes include increased lung CD4 T cells, increased Th2 cytokine expression, and airway goblet cell hyperplasia. Furthermore, coinfected mice exhibited significantly more airspace neutrophil infiltration at 6 hours following P. aeruginosa infection and exhibited an improved rate of survival compared with bacterial infected alone. These results suggest that chronic helminth infection of the intestines can influence and enhance acute airway neutrophil responses to P. aeruginosa infection.
Topics: Animals; Helminthiasis; Inflammation Mediators; Intestinal Diseases, Parasitic; Lung; Mice; Mice, Inbred C57BL; Nematospiroides dubius; Neutrophils; Pseudomonas aeruginosa; Th2 Cells
PubMed: 31673002
DOI: 10.1038/s41598-019-51991-3 -
Viruses Sep 2019Influenza viruses are important pathogens causing respiratory disease in humans and animals. In contrast to influenza A virus (IAV) that can infect a wide range of...
Influenza viruses are important pathogens causing respiratory disease in humans and animals. In contrast to influenza A virus (IAV) that can infect a wide range of animal species, other influenza viruses, including influenza B virus (IBV), influenza C virus (ICV), and influenza D virus (IDV) have a limited host range. Swine can be infected with all four different genera of influenza viruses. IAV infection of pigs causes the well-known swine influenza that poses significant threats to human and animal health. However, influenza virus infection of pigs with IBV, ICV, and IDV are not well-characterized. Herein, we compared pathogenicity of IBV and IDV using intratracheal and intranasal infection of pigs, which are IAV seropositive, and commingled naïve pigs with the infected animals to determine their transmissibility. Both viruses caused fever and some lung lesions, replicated in the lungs of infected pigs, but only IDV transmitted to the contact animals. Although IBV and IDV displayed differing levels of replication in the respiratory tract of infected pigs, no significant differences in pathogenicity of both viruses were observed. These results indicate that both IBV and IDV can replicate, and are pathogenic in pigs.
Topics: Animals; Disease Models, Animal; Host Specificity; Influenza A virus; Influenza B virus; Gammainfluenzavirus; Lung; Orthomyxoviridae Infections; Swine; Swine Diseases; Thogotovirus; United States; Viral Load; Virulence; Virus Replication
PubMed: 31569752
DOI: 10.3390/v11100905 -
Biodiverse Species Elicit Distinct Patterns of Pulmonary Inflammation following Sublethal Infection.MSphere Aug 2020is an endemic dimorphic fungus that can cause disease in healthy and immunocompromised individuals after the transition of inhaled spores into the facultative...
is an endemic dimorphic fungus that can cause disease in healthy and immunocompromised individuals after the transition of inhaled spores into the facultative intracellular yeast form. There is substantial diversity among species, but it is not clear how this heterogeneity impacts the progression of pathology and cellular immune responses during acute respiratory infection, which represents the vast majority of histoplasmosis disease burden. After inoculating mice intranasally with a sublethal inoculum, we characterized the immune response to (strain G186A) and (strain G217B) using comprehensive flow cytometric and single-cell analyses. Within 8 days after inoculation, induced a significantly higher infiltration of neutrophils and inflammatory monocytes into the lung compared to Microscopic analysis of infected lung tissue revealed that although the total number of fungi was similar within inflamed lung lesions, we observed different species-dependent intracellular yeast distribution patterns. Inoculation with -expressing strains indicated that , but not , was associated primarily with alveolar macrophages early after infection. Interestingly, we observed a significant reduction in the total number of alveolar macrophages 12 to 16 days after but not infection, despite similar intracellular growth dynamics within AMJ2-C11 alveolar macrophages Together, our data suggest that , but not , preferentially interacts with alveolar macrophages early after infection, which may lead to a different course of inflammation and resolution despite similar rates of fungal clearance. Acute pulmonary histoplasmosis in healthy individuals comprises most of the disease burden caused by the fungal pathogen Fungal pneumonia is frequently delayed in diagnosis and treatment due to a prolonged period of quiescence early during infection. In this study, we used a murine respiratory model of histoplasmosis to investigate how different species modulate lung inflammation throughout the complete course of infection. We propose that a relatively low, sublethal inoculum is ideal to model acute pulmonary histoplasmosis in humans, primarily due to the quiescent stage of fungal growth that occurs in the lungs of mice prior to the initiation of inflammation. Our results reveal the unique course of lung immunity associated with divergent species of and imply that the progression of clinical disease is considerably more heterogeneous than previously recognized.
Topics: Animals; Disease Models, Animal; Flow Cytometry; Genetic Variation; Histoplasma; Histoplasmosis; Lung; Macrophages, Alveolar; Male; Mice; Mice, Inbred C57BL; Pneumonia
PubMed: 32848006
DOI: 10.1128/mSphere.00742-20 -
Infection and Immunity Jul 2019Pulmonary pathogens encounter numerous insults, including phagocytic cells designed to degrade bacteria, while establishing infection in the human lung. is a versatile,...
Pulmonary pathogens encounter numerous insults, including phagocytic cells designed to degrade bacteria, while establishing infection in the human lung. is a versatile, opportunistic pathogen that can cause severe pneumonia, and methicillin-resistant isolates are of particular concern. Recent reports present conflicting data regarding the ability of to survive and replicate within macrophages. However, due to use of multiple strains and macrophage sources, making comparisons between reports remains difficult. Here, we established a disease-relevant platform to study innate interactions between and human lungs. uman recision-ut ung lices (hPCLS) were subjected to infection by LAC (methicillin-resistant) or UAMS-1 (methicillin-sensitive) isolates. Additionally, primary human alveolar macrophages (hAMs) were infected with , and antibacterial activity was assessed. Although both isolates survived within hAM phagosomes, neither strain replicated efficiently in these cells. was prevalent within the epithelial and interstitial regions of hPCLS, with limited numbers present in a subset of hAMs, suggesting that the pathogen may not target phagocytic cells for intracellular growth during natural pulmonary infection. -infected hAMs mounted a robust inflammatory response that reflected natural human disease. LAC was significantly more cytotoxic to hAMs than UAMS-1, potentially due to isolate-specific virulence factors. The bicomponent toxin Panton-Valentine leukocidin was not produced during intracellular infection, while alpha-hemolysin was produced but was not hemolytic, suggesting that hAMs alter toxin activity. Overall, this study defined a new disease-relevant infection platform to study interaction with human lungs and to define virulence factors that incapacitate pulmonary cells.
Topics: Anti-Bacterial Agents; Bacterial Toxins; Exotoxins; Humans; Leukocidins; Lung; Macrophages, Alveolar; Phagosomes; Staphylococcal Infections; Staphylococcus aureus; Virulence Factors
PubMed: 31010814
DOI: 10.1128/IAI.00167-19 -
Virology Dec 2020Mammalian orthoreovirus (MRV) infections are ubiquitous in mammals. Increasing evidence suggests that some MRVs can cause severe respiratory disease and encephalitis in...
Mammalian orthoreovirus (MRV) infections are ubiquitous in mammals. Increasing evidence suggests that some MRVs can cause severe respiratory disease and encephalitis in humans and other animals. Previously, we isolated six bat MRV strains. However, the pathogenicity of these bat viruses remains unclear. In this study, we investigated the host range and pathogenicity of 3 bat MRV strains (WIV2, 3 and 7) which represent three serotypes. Our results showed that all of them can infect cell lines from different mammalian species and displayed different replication efficiency. The BALB/c mice infected by bat MRVs showed clinical symptoms with systematic infection especially in lung and intestines. Obvious tissue damage were found in all infected lungs. One of the strains, WIV7, showed higher replication efficiency in vitro and vivo and more severe pathogenesis in mice. Our results provide new evidence showing potential pathogenicity of bat MRVs in animals and probable risk in humans.
Topics: Animals; Cell Line; Chiroptera; Female; Host Specificity; Humans; Intestines; Lung; Mice; Mice, Inbred BALB C; Orthoreovirus, Mammalian; Pneumonia, Viral; Reoviridae Infections; Serogroup
PubMed: 32859395
DOI: 10.1016/j.virol.2020.05.014 -
BioMed Research International 2015Respiratory syncytial virus is a worldwide pathogen agent responsible for frequent respiratory tract infections that may become severe and potentially lethal in high... (Review)
Review
Respiratory syncytial virus is a worldwide pathogen agent responsible for frequent respiratory tract infections that may become severe and potentially lethal in high risk infants and adults. Several studies have been performed to investigate the immune response that determines the clinical course of the infection. In the present paper, we review the literature on viral, environmental, and host factors influencing virus response; the mechanisms of the immune response; and the action of nonimmunological factors. These mechanisms have often been studied in animal models and in the present review we also summarize the main findings obtained from animal models as well as the limits of each of these models. Understanding the lung response involved in the pathogenesis of these respiratory infections could be useful in improving the preventive strategies against respiratory syncytial virus.
Topics: Humans; Immunity, Innate; Lung; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections
PubMed: 26064963
DOI: 10.1155/2015/875723 -
Journal of Infection in Developing... Jul 2014Camels migrate between the open boundaries of Sudan and Egypt either for grazing or for slaughtering. Bad hygiene and stress is often related to pulmonary diseases in...
INTRODUCTION
Camels migrate between the open boundaries of Sudan and Egypt either for grazing or for slaughtering. Bad hygiene and stress is often related to pulmonary diseases in camels. This study investigated whether camels slaughtered in Cairo carried pulmonary infections.
METHODOLOGY
Five hundred lung tissues of slaughtered camels were examined and 100 samples suspected for pulmonary infection were subjected to microbial identification and histopathology.
RESULTS
A total of 70 lung tissues revealed 97 bacterial isolates of 8 species, including Staphylococcus aureus (37.14%), Escherichia coli (27.14%), Klebsiella pneumoniae (26.71%), Bacillus spp. (25.72%), Streptococcus pyogenes (10%), Corynebacterium spp. (8.85 %), Pasteurella spp. (2.85%), and Arcanobacterium pyogenes (1.4%). Some of these species were earlier reported to be associated with pulmonary infection. Histopathology revealed different types of pneumonia in 50% of the investigated lungs.
CONCLUSIONS
A considerable number of apparently healthy camels carry pathogenic agents in their lower respiratory tracts. Immunosuppression and stressful conditions might influence these pathogens to induce respiratory diseases in camels. Thus, the infected camels might act as reservoir of these infections agents. If adequate care is not taken, this might be a threat to abattoir workers and may spread infections to humans.
Topics: Abattoirs; Animal Diseases; Animals; Asymptomatic Infections; Camelus; Corynebacterium; Egypt; Escherichia coli; Klebsiella pneumoniae; Lung; Lung Diseases; Staphylococcus aureus; Streptococcus pyogenes
PubMed: 25022303
DOI: 10.3855/jidc.4810 -
American Journal of Transplantation :... Apr 2016Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for... (Comparative Study)
Comparative Study
Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high-dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics. A quantitative decrease in bacterial counts in bronchoalveolar lavage (BAL) was found in all antibiotic-treated cases but in only two control cases. Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group. EVLP with broad-spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance. Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α, IL-1β and macrophage inflammatory proteins 1α and 1β at 12 h. In conclusion, EVLP treatment of infected donor lungs with broad-spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function.
Topics: Adult; Anti-Infective Agents; Bacterial Load; Bronchoalveolar Lavage Fluid; Bronchopneumonia; Case-Control Studies; Extracorporeal Circulation; Female; Follow-Up Studies; Humans; Lung; Lung Transplantation; Male; Middle Aged; Perfusion; Prognosis; Tissue Donors; Tissue and Organ Procurement
PubMed: 26730551
DOI: 10.1111/ajt.13562 -
MSphere Mar 2021Enterovirus 71 (EV71) can cause a severe hand-foot-mouth disease in children. However, the precise mechanism of EV71-associated disease, particularly the...
Enterovirus 71 (EV71) can cause a severe hand-foot-mouth disease in children. However, the precise mechanism of EV71-associated disease, particularly the neuropathogenesis and pulmonary disorder, is still not fully understood because no suitable animal models are available. The human scavenger receptor class B, member 2 (hSCARB2), is a cellular receptor for EV71. Here, we generated a novel knock-in (KI) mouse model using the CRISPR/Cas9 system to insert the hSCARB2 gene into the mouse locus to study the pathogenesis of EV71. The hSCARB2 KI mice infected with clinical isolates of EV71 showed neurological symptoms, such as ataxia, paralysis, and death. Viral replication was detected in mainly astrocytes and a limited number of neurons and microglia, accompanied by gliosis. Vascular leakage and alveoli filled with erythrocytes were detected, suggesting that edema and hemorrhage, which are observed in human patients, also occurred in EV71-infected KI mice. In addition, proinflammatory cytokines and chemokines were significantly increased in the serum of infected KI mice. These pathological features of the KI mice after infection resembled those of EV71 encephalomyelitis in humans. Therefore, our KI mouse model is suitable to study the pathogenesis of EV71 and is of great significance for development of antiviral drugs and vaccines to treat or prevent EV71 infection. Enterovirus 71 (EV71) is associated with severe hand-foot-mouth disease. Recently, outbreaks of EV71 infection with high mortality have been reported in the Asia-Pacific region, posing a great challenge for global public health. To date, the precise mechanism of EV71-induced disease, particularly the neuropathogenesis and respiratory disorders, is still not fully understood because no suitable animal models are available. Human scavenger receptor class B, member 2 (hSCARB2), has been identified as a cellular receptor for EV71. Here, we introduce a novel CRISPR/Cas9-mediated hSCARB2 knock-in (KI) mouse model for the study of EV71 pathogenesis, which is of great significance for the development of antiviral drugs and vaccines.
Topics: Animals; Astrocytes; CRISPR-Cas Systems; Disease Models, Animal; Enterovirus A, Human; Enterovirus Infections; Female; Gene Knock-In Techniques; Hand, Foot and Mouth Disease; Humans; Lung; Lysosomal Membrane Proteins; Male; Mice; Mice, Inbred C57BL; Nervous System Diseases; Receptors, Scavenger
PubMed: 33692197
DOI: 10.1128/mSphere.01048-20 -
Infection and Immunity Mar 2020is a Gram-negative bacterium found ubiquitously in the environment that has historically been regarded as nonpathogenic. is increasingly observed in patient sputa in...
is a Gram-negative bacterium found ubiquitously in the environment that has historically been regarded as nonpathogenic. is increasingly observed in patient sputa in cystic fibrosis (CF), and while existing epidemiology indicates that patients with have poorer diagnoses, its clinical significance remains unclear. Moreover, as multidrug resistance is common among isolates, treatment options for these infections may be limited. Here, we investigated the pathogenicity of alone and during polymicrobial infection with Colonization, persistence, and virulence of were assessed in experimental respiratory infections of mice. The results of this study indicate that transiently colonizes the lung accompanied by significant weight loss and immune cell infiltration and the expression of early inflammatory markers, including interleukin 6 (IL-6), IL-1α, and tumor necrosis factor alpha (TNF-α). Importantly, polymicrobial infection with elicited significantly higher counts in bronchoalveolar lavages and lung tissue homogenates. This increase in bacterial load was directly correlated with the density of the population and required viable bacteria. Microscopic analysis of biofilms formed revealed that formed well-integrated biofilms with , and these organisms colocalize in the lung during dual-species infection. Based on these results, we conclude that active cellular processes by afford a significant benefit to during polymicrobial infections. Furthermore, these results indicate that may have clinical significance in respiratory infections.
Topics: Animals; Bacterial Load; Body Weight; Bronchoalveolar Lavage Fluid; Coinfection; Disease Models, Animal; Gram-Negative Bacterial Infections; Immunity, Innate; Lung; Mice; Microbial Interactions; Pneumonia, Bacterial; Pseudomonas aeruginosa; Stenotrophomonas maltophilia
PubMed: 31932329
DOI: 10.1128/IAI.00855-19