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Parasites, Hosts and Diseases May 2024We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three...
We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (n=5 each) were orally administered 1,000 T. canis 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (n=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with T. canis exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of T. canis larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to T. canis infection in mice, which may have implications to further understand human toxocariasis.
Topics: Animals; Toxocara canis; Toxocariasis; Mice, Inbred BALB C; Larva; Mice; Cytokines; Lung; Liver; Brain; Bronchoalveolar Lavage Fluid; Female; Parasite Load; Eye; Disease Models, Animal
PubMed: 38835265
DOI: 10.3347/PHD.23125 -
Italian Journal of Pediatrics Jun 2024Lysinuric protein intolerance (LPI) is a multi-organ metabolic disorder characterized by the imbalance in absorption and excretion of cationic amino acids like lysine,...
BACKGROUND
Lysinuric protein intolerance (LPI) is a multi-organ metabolic disorder characterized by the imbalance in absorption and excretion of cationic amino acids like lysine, ornithine and arginine. Infants with LPI typically present with recurrent vomiting, poor growth, interstitial lung disease or renal impairment. The early onset of pulmonary alveolar proteinosis (PAP) has been reported to be associated with a severe form of LPI. Treatment of PAP most commonly consists of whole-lung lavage (WLL) and in autoimmune PAP, granulocyte-macrophage colony stimulating factor (GM-CSF) administration. Nevertheless, GM-CSF therapy in LPI-associated PAP has not been scientifically justified.
CASE PRESENTATION
We describe the case of an 8-month-old infant presenting with respiratory failure due to LPI associated with PAP, who was twice treated with WLL; firstly, while on veno-venous ECMO assistance and then by the use of a selective bronchial blocker. After the two treatments with WLL, she was weaned from daytime respiratory support while on initially subcutaneous, then on inhaled GM-CSF therapy.
CONCLUSIONS
This case supports the notion that GM-CSF therapy might be of benefit in patients with LPI-associated PAP. Further studies are needed to clarify the exact mechanism of GM-CSF in patients with LPI-associated PAP.
Topics: Humans; Pulmonary Alveolar Proteinosis; Granulocyte-Macrophage Colony-Stimulating Factor; Infant; Female; Bronchoalveolar Lavage; Amino Acid Metabolism, Inborn Errors
PubMed: 38831374
DOI: 10.1186/s13052-024-01677-y -
Frontiers in Immunology 2024Persistent radiological lung abnormalities are evident in many survivors of acute coronavirus disease 2019 (COVID-19). Consolidation and ground glass opacities are...
BACKGROUND
Persistent radiological lung abnormalities are evident in many survivors of acute coronavirus disease 2019 (COVID-19). Consolidation and ground glass opacities are interpreted to indicate subacute inflammation whereas reticulation is thought to reflect fibrosis. We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis.
METHODS
We compared single-cell transcriptomic profiles and T cell receptor (TCR) repertoires of bronchoalveolar cells obtained from convalescent individuals with each radiological pattern, targeting lung segments affected by the predominant abnormality.
RESULTS
CD4 central memory T cells and CD8 effector memory T cells were significantly more abundant in those with inflammatory radiology. Clustering of similar TCRs from multiple donors was a striking feature of both phenotypes, consistent with tissue localised antigen-specific immune responses. There was no enrichment for known SARS-CoV-2-reactive TCRs, raising the possibility of T cell-mediated immunopathology driven by failure in immune self-tolerance.
CONCLUSIONS
Post-COVID radiological inflammation and fibrosis show evidence of shared antigen-specific T cell responses, suggesting a role for therapies targeting T cells in limiting post-COVID lung damage.
Topics: Humans; COVID-19; Single-Cell Analysis; SARS-CoV-2; Male; Female; Middle Aged; Receptors, Antigen, T-Cell; Pulmonary Fibrosis; CD8-Positive T-Lymphocytes; CD4-Positive T-Lymphocytes; Lung; Aged; Adult; Inflammation; Bronchoalveolar Lavage Fluid; Memory T Cells; Transcriptome
PubMed: 38827740
DOI: 10.3389/fimmu.2024.1372658 -
Medical Mycology Journal 2024Mucormycosis is a fungal infectious disease caused by Rhizopus oryzae and other members of the order Mucorales, and it is known as one of the most lethal fungal...
Mucormycosis is a fungal infectious disease caused by Rhizopus oryzae and other members of the order Mucorales, and it is known as one of the most lethal fungal infections. Early diagnosis of mucormycosis improves prognosis because of limited effective treatments and the rapid progression of the disease. On the other hand, the lack of characteristic clinical findings in mucormycosis and the challenge of early definitive diagnosis make early treatment difficult. Our goal was to establish a serodiagnostic method to detect Rhizopus specific antigen (RSA), and we have developed a diagnostic kit by Enzyme-linked immuno-sorbent assay (ELISA) using a monoclonal antibody against this antigen. RSA increased over time in the serum and alveolar lavage fluid of R. oryzae-infected mice. RSA was also detected in serum and alveolar fluid, even at an early stage (Day 1), when the tissue invasion of R. oryzae mycelium was not histopathologically detectable in the lungs of R. oryzae-infected mice. Further evaluation is needed to determine the feasibility of using this assay in clinical practice.
Topics: Mucormycosis; Animals; Mice; Enzyme-Linked Immunosorbent Assay; Antigens, Fungal; Rhizopus oryzae; Biomarkers; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Antibodies, Monoclonal; Rhizopus; Lung; Humans; Serologic Tests
PubMed: 38825527
DOI: 10.3314/mmj.24.002 -
Ecotoxicology and Environmental Safety Jul 2024The correlation between formaldehyde (FA) exposure and prevalence of asthma has been widely reported. However, the underlying mechanism is still not fully understood. FA...
The correlation between formaldehyde (FA) exposure and prevalence of asthma has been widely reported. However, the underlying mechanism is still not fully understood. FA exposure at 2.0 mg/m was found to exacerbate asthma in OVA-induced murine models. IFN-γ, the cytokine produced by T helper 1 (Th1) cells, was significantly induced by FA in serum and bronchoalveolar lavage fluid (BALF) of asthmatic mice, which was different from cytokines secreted by other Th cells. The observation was also confirmed by mRNA levels of Th marker genes in CD4+ T cells isolated from BALF. In addition, increased production of IFN-γ and expression of T-bet in Jurkat T cells primed with phorbol ester and phytohaemagglutinin were also observed with 100 μM FA treatment in vitro. Upregulated STAT1 phosphorylation, T-bet expression and IFN-γ production induced by FA was found to be restrained by STAT1 inhibitor fludarabine, indicating that FA promoted Th1 commitment through the autocrine IFN-γ/STAT1/T-bet pathway in asthma. This work not only revealed that FA could bias Th lineage commitment to exacerbate allergic asthma, but also identified the signaling mechanism of FA-induced Th1 differentiation, which may be utilized as the target for development of interfering strategies against FA-induced immune disorders.
Topics: Asthma; Animals; STAT1 Transcription Factor; Interferon-gamma; Mice; T-Box Domain Proteins; Formaldehyde; Inflammation; Mice, Inbred BALB C; Humans; Female; Bronchoalveolar Lavage Fluid; T-Lymphocytes, Helper-Inducer; Signal Transduction; Th1 Cells; Jurkat Cells
PubMed: 38823345
DOI: 10.1016/j.ecoenv.2024.116534 -
Acta Veterinaria Scandinavica May 2024A syndrome of acute non-cardiogenic pulmonary edema associated with hunting is prevalent in the drever breed, but etiology of this syndrome is currently unknown....
BACKGROUND
A syndrome of acute non-cardiogenic pulmonary edema associated with hunting is prevalent in the drever breed, but etiology of this syndrome is currently unknown. Alveolar surfactant has a critical role in preventing alveolar collapse and edema formation. The aim of this study was to investigate, whether the predisposition to hunting associated pulmonary edema in drever dogs is associated with impaired biophysical properties of alveolar surfactant. Seven privately owned drever dogs with recurrent hunting associated pulmonary edema and seven healthy control dogs of other breeds were included in the study. All affected dogs underwent thorough clinical examinations including echocardiography, laryngeal evaluation, bronchoscopy, and bronchoalveolar lavage (BAL) as well as head, neck and thoracic computed tomography imaging to rule out other cardiorespiratory diseases potentially causing the clinical signs. Alveolar surfactant was isolated from frozen, cell-free supernatants of BAL fluid and biophysical analysis of the samples was completed using a constrained sessile drop surfactometer. Statistical comparisons over consecutive compression expansion cycles were performed using repeated measures ANOVA and comparisons of single values between groups were analyzed using T-test.
RESULTS
There were no significant differences between groups in any of the biophysical outcomes of surfactant analysis. The critical function of surfactant, reducing the surface tension to low values upon compression, was similar between healthy dogs and affected drevers.
CONCLUSIONS
The etiology of hunting associated pulmonary edema in drever dogs is not due to an underlying surfactant dysfunction.
Topics: Animals; Dogs; Pulmonary Edema; Dog Diseases; Pulmonary Surfactants; Male; Female; Bronchoalveolar Lavage Fluid; Case-Control Studies
PubMed: 38822358
DOI: 10.1186/s13028-024-00745-x -
Veterinary Immunology and... Jul 2024Influenza A virus (IAV) is a major pathogen in the swine industry. Whole-inactivated virus (WIV) vaccines in swine are highly effective against homologous viruses but...
Influenza A virus (IAV) is a major pathogen in the swine industry. Whole-inactivated virus (WIV) vaccines in swine are highly effective against homologous viruses but provide limited protection to antigenically divergent viruses and may lead to vaccine-associated enhanced respiratory disease (VAERD) after heterologous infection. Although VAERD is reproducible in laboratory studies, clinical diagnosis is challenging, as it would require both knowledge of prior vaccine history and evidence of severe disease by assessment of pathologic lesions at necropsy following infection with a heterologous virus. The objective of this study was to identify potential biomarkers for VAERD for antemortem clinical diagnosis. Naïve pigs were split into two groups, and one group was vaccinated with IAV WIV vaccine. All pigs were then challenged with a heterologous virus to induce VAERD in the vaccinated group and necropsied at 5 days post infection (dpi). Blood was collected on 0, 1, 3, and 5 dpi, and assessed by hematology, plasma chemistry, acute phase proteins, and citrullinated H3 histone (CitH3) assays. Additionally, cytokine and CitH3 levels were assessed in bronchoalveolar lavage fluid (BALF) collected at necropsy. Compared to nonvaccinated challenged pigs, blood collected from vaccinated and challenged (V/C) pigs with VAERD had elevated white blood cells and neutrophils, elevated C-reactive protein and haptoglobin acute phase proteins, and elevated CitH3. In BALF, the proinflammatory cytokine IL-8 and CitH3 were elevated in V/C pigs. In conclusion, a profile of elevated white blood cells and neutrophils, elevated C-reactive protein and haptoglobin, and elevated CitH3 may be relevant for a clinical antemortem IAV VAERD diagnosis.
Topics: Animals; Swine; Orthomyxoviridae Infections; Swine Diseases; Influenza Vaccines; Biomarkers; Influenza A virus; Bronchoalveolar Lavage Fluid; Cytokines; Vaccines, Inactivated
PubMed: 38815504
DOI: 10.1016/j.vetimm.2024.110787 -
Molecular Biology Reports May 2024Existing investigations suggest that the blockade of phosphoinositide 3-kinase (PI3K) activity contributes to inflammatory solution in allergic asthma, but whether this...
Inhibition of phosphoinositide 3-kinase activity attenuates neutrophilic airway inflammation and inhibits pyrin domain-containing 3 inflammasome activation in an ovalbumin-lipopolysaccharide-induced asthma murine model.
BACKGROUND
Existing investigations suggest that the blockade of phosphoinositide 3-kinase (PI3K) activity contributes to inflammatory solution in allergic asthma, but whether this inhibition directly attenuates neutrophilic airway inflammation in vivo is still unclear. We explored the pharmacological effects of LY294002, a specific inhibitor of PI3K on the progression of neutrophilic airway inflammation and investigated the underlying mechanism.
METHODS AND RESULTS
Female C57BL/6 mice were intranasally sensitized with ovalbumin (OVA) together with lipopolysaccharide (LPS) on days 0 and 6, and challenged with OVA on days 14-17 to establish a neutrophilic airway disease model. In the challenge phase, a subset of mice was treated intratracheally with LY294002. We found that treatment of LY294002 attenuates clinic symptoms of inflammatory mice. Histological studies showed that LY294002 significantly inhibited inflammatory cell infiltration and mucus production. The treatment also significantly inhibited OVA-LPS induced increases in inflammatory cell counts, especially neutrophil counts, and IL-17 levels in bronchoalveolar lavage fluid (BALF). LY294002 treated mice exhibited significantly increased IL-10 levels in BALF compared to the untreated mice. In addition, LY294002 reduced the plasma concentrations of IL-6 and IL-17. The anti-inflammatory effects of LY29402 were correlated with the downregulation of NLRP3 inflammasome.
CONCLUSIONS
Our findings suggested that LY294002 as a potential pharmacological target for neutrophilic airway inflammation.
Topics: Animals; Asthma; Ovalbumin; Lipopolysaccharides; Mice; Inflammasomes; Disease Models, Animal; Female; NLR Family, Pyrin Domain-Containing 3 Protein; Chromones; Morpholines; Neutrophils; Phosphoinositide-3 Kinase Inhibitors; Bronchoalveolar Lavage Fluid; Phosphatidylinositol 3-Kinases; Mice, Inbred C57BL; Inflammation; Lung; Interleukin-17
PubMed: 38811424
DOI: 10.1007/s11033-024-09360-5 -
Animal Models and Experimental Medicine May 2024Glaucoma, an irreversible optic neuropathy, primarily affects retinal ganglion cells (RGC) and causes vision loss and blindness. The damage to RGCs in glaucoma occurs by... (Review)
Review
Glaucoma, an irreversible optic neuropathy, primarily affects retinal ganglion cells (RGC) and causes vision loss and blindness. The damage to RGCs in glaucoma occurs by various mechanisms, including elevated intraocular pressure, oxidative stress, inflammation, and other neurodegenerative processes. As the disease progresses, the loss of RGCs leads to vision loss. Therefore, protecting RGCs from damage and promoting their survival are important goals in managing glaucoma. In this regard, resveratrol (RES), a polyphenolic phytoalexin, exerts antioxidant effects and slows down the evolution and progression of glaucoma. The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina. Additionally, RES plays protective roles in RGCs by promoting cell growth, reducing apoptosis, and decreasing oxidative stress in HO-exposed RGCs. RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways. RES could alleviate retinal function impairment by suppressing the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway. Therefore, RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.
PubMed: 38808561
DOI: 10.1002/ame2.12438 -
Clinical and Translational Science Jun 2024Cold-inducible RNA-binding protein (CIRP) is a damage-associated molecular pattern that plays a critical role in triggering inflammatory responses. It remains unknown...
Cold-inducible RNA-binding protein (CIRP) is a damage-associated molecular pattern that plays a critical role in triggering inflammatory responses. It remains unknown whether CIRP is strongly associated with bacterial load, inflammatory response, and mortality in sepsis model. Pneumonia was induced in specific pathogen-free 8-9-week old male rats by injecting bacteria via puncture of the tracheal cartilage. The expressions of CIRP and proinflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β] in lung tissues, alveolar macrophages (AMs), plasma, and bronchoalveolar lavage fluid (BALF) were determined by reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The numbers of bacteria recovered from the lungs were correlated with the bacterial loads injected and mortality. The expressions of CIRP increased sharply as the bacterial loads increased in the lung tissues and AMs. The amounts of TNF-α, IL-6 and IL-1β proteins synthesized were dependent on the bacterial load in the lung tissues. Releases of CIRP, TNF-α, IL-6, and IL-1β increased with the bacterial load in the blood plasma. The proteins confirmed similar patterns in the BALF. CIRP was strongly associated with the releases of TNF-α, IL-6, and IL-1β in the lung tissues, blood plasma, and BALF, and showed a close correlation with mortality. CIRP demonstrated a strong association with bacterial load, which is new evidence, and close correlations with proinflammatory cytokines and mortality of pneumonia in rats, suggesting that it might be an interesting pneumonic biomarker for monitoring host response and predicting mortality, and a promising target for immunotherapy.
Topics: Animals; Male; RNA-Binding Proteins; Cytokines; Bacterial Load; Rats; Lung; Bronchoalveolar Lavage Fluid; Macrophages, Alveolar; Pneumonia; Rats, Sprague-Dawley; Interleukin-1beta; Disease Models, Animal; Inflammation Mediators; Tumor Necrosis Factor-alpha; Pneumonia, Bacterial
PubMed: 38807464
DOI: 10.1111/cts.13850