scholarly journals AscarisLarval Infection and Lung Invasion Directly Induce Severe Allergic Airway Disease in Mice

2018 ◽  
Vol 86 (12) ◽  
Author(s):  
Jill E. Weatherhead ◽  
Paul Porter ◽  
Amy Coffey ◽  
Dana Haydel ◽  
Leroy Versteeg ◽  
...  
Keyword(s):  
Airway Remodeling ◽  
Periodic Acid ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Interleukin 4 ◽  
Lung Pathology ◽  
Periodic Acid Schiff ◽  
Content Type ◽  
Larval Migration

ABSTRACTAscaris lumbricoides(roundworm) is the most common helminth infection globally and a cause of lifelong morbidity that may include allergic airway disease, an asthma phenotype. We hypothesize thatAscarislarval migration through the lungs leads to persistent airway hyperresponsiveness (AHR) and type 2 inflammatory lung pathology despite resolution of infection that resembles allergic airway disease. Mice were infected withAscarisby oral gavage. Lung AHR was measured by plethysmography and histopathology with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stains, and cytokine concentrations were measured by using Luminex Magpix.Ascaris-infected mice were compared to controls or mice with allergic airway disease induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA).Ascaris-infected mice developed profound AHR starting at day 8 postinfection (p.i.), peaking at day 12 p.i. and persisting through day 21 p.i., despite resolution of infection, which was significantly increased compared to controls and OVA/OVA mice.Ascaris-infected mice had a robust type 2 cytokine response in both the bronchoalveolar lavage (BAL) fluid and lung tissue, similar to that of the OVA/OVA mice, including interleukin-4 (IL-4) (P < 0.01 andP< 0.01, respectively), IL-5 (P < 0.001 andP < 0.001), and IL-13 (P < 0.001 andP < 0.01), compared to controls. By histopathology,Ascaris-infected mice demonstrated early airway remodeling similar to, but more profound than, that in OVA/OVA mice. We found thatAscarislarval migration causes significant pulmonary damage, including AHR and type 2 inflammatory lung pathology that resembles an extreme form of allergic airway disease. Our findings indicate that ascariasis may be an important cause of allergic airway disease in regions of endemicity.

Chitinase 3-like-1 protects airway function despite promoting type 2 inflammation during fungal-associated allergic airway inflammation

2021 ◽  
Author(s):  
Joseph J. Mackel ◽  
Jaleesa M. Garth ◽  
MaryJane Jones ◽  
Diandra A. Ellis ◽  
Jonathan P. Blackburn ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Periodic Acid ◽  
Acute Infection ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Allergic Airway Inflammation ◽  
Lung Edema ◽  
Periodic Acid Schiff ◽  
Wide Range ◽  
Type 2 Inflammation

Exposure to fungi can result in a wide range of comorbidities depending on the immune status of the host. Chronic exposure and reactivity to fungi such as Aspergillus fumigatus can result in conditions such as severe asthma with fungal sensitization (SAFS) or allergic bronchopulmonary aspergillosis (ABPA). However, the pathophysiology of SAFS and ABPA are not well understood. Here, we report that the chitinase-like protein YKL-40 is elevated in lung lavage fluid from human asthmatics that are sensitized to fungi. Initial studies demonstrated that mice deficient in the murine ortholog of YKL-40, breast regression protein-39 (BRP-39, chitinase-3-like 1, Chi3l1), were not more susceptible to acute infection with A. fumigatus. However, in an experimental model of fungal-associated allergic airway inflammation (fungal asthma), Chi3l1-/- mice had significantly increased airway hyperresponsiveness (AHR). Surprisingly, increased AHR in Chi3l1-/- mice occurred in the presence of significantly lower type 2 responses (decreased eosinophil numbers and decreased IL-4, IL-5, IL-33, CCL17 and CCL22 levels), although type 1 and type 17 responses were not different. Increased AHR was not associated with differences in Periodic-acid-Schiff staining of lung tissue, differences in the expression of Muc5ac and Clca3, nor differences in lung edema. Bone marrow chimera studies revealed that the presence of BRP-39 in either the hematopoietic or non-hematopoietic compartment was sufficient for controlling AHR during fungal asthma. Collectively, these results indicate that BRP-39 protects against AHR during fungal asthma despite contributing to type 2 inflammation, thus highlighting an unexpected protective role for BRP-39 in allergic fungal asthma.

Enterogenous cyst in the cervical spinal canal

1988 ◽  
Vol 68 (2) ◽  
pp. 292-296 ◽  
Author(s):  
Kouichi Miyagi ◽  
Jiro Mukawa ◽  
Susumu Mekaru ◽  
Yasunari Ishikawa ◽  
Toshihiko Kinjo ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Immunohistochemical Staining ◽  
Periodic Acid ◽  
Enterogenous Cyst ◽  
Resonance Imaging ◽  
Periodic Acid Schiff ◽  
Content Type ◽  
Low Intensity ◽  
Old Japanese ◽  
Fine Print

✓ The case of an 11-year-old Japanese girl with an intradural and extramedullary enterogenous cyst is presented. A mass giving a low-intensity signal in comparison with the spinal cord was demonstrated on magnetic resonance imaging. Histologically, the diagnosis was confirmed on specimens stained with periodic acid-Schiff, alcian blue, mucicarmine, and immunohistochemical staining of carcinoembryonic antigen, and by electron microscopy.

scholarly journals Matricellular Protein Periostin Promotes Pericyte Migration in Fibrotic Airways

2021 ◽  
Vol 2 ◽  
Author(s):  
Rebecca E. Bignold ◽  
Jill R. Johnson
Keyword(s):  
Allergic Asthma ◽  
Airway Remodeling ◽  
Airway Disease ◽  
Lavage Fluid ◽  
Allergic Airway Disease ◽  
Matricellular Protein ◽  
Large Airways ◽  
Migration Assays ◽  
Fibrotic Lung Disease

Introduction: Periostin is a matricellular protein that is currently used as a biomarker for asthma. However, its contribution to tissue remodeling in allergic asthma is currently unknown. We have previously demonstrated that tissue-resident mesenchymal stem cells known as pericytes are a key cell type involved in airway remodeling. This is thought to be caused the uncoupling of pericytes from the microvasculature supporting the large airways, facilitated by inflammatory growth factors and cytokines. It is hypothesized that periostin may be produced by profibrotic pericytes and contribute to the remodeling observed in allergic asthma.Methods: Lung sections from mice with allergic airway disease driven by exposure to house dust mite (HDM) were stained using an anti-periostin antibody to explore its involvement in fibrotic lung disease. Human pericytes were cultured in vitro and stained for periostin to assess periostin expression. Migration assays were performed using human pericytes that were pretreated with TGF-β or periostin. ELISAs were also carried out to assess periostin expression levels in bronchoalveolar lavage fluid as well as the induction of periostin production by IL-13.Results: Immunostaining indicated that pericytes robustly express periostin, with increased expression following treatment with TGF-β. Migration assays demonstrated that pericytes treated with periostin were more migratory. Periostin production was also increased in HDM exposed mice as well as in cultured pericytes treated with IL-13.Conclusion: Periostin is produced by pericytes in response to TGF-β or IL-13, and periostin plays a key role in inducing pericyte migration. The increase in periostin expression in TGF-β or IL-13 treated pericytes suggests that IL-13 may trigger periostin production in pericytes whilst TGF-β modulates periostin expression to promote pericyte migration in the context of tissue fibrosis.

scholarly journals Eyedrop Inoculation Causes Sublethal Leptospirosis in Mice

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Joseph Pierce Sullivan ◽  
Nisha Nair ◽  
Hari-Hara Potula ◽  
Maria Gomes-Solecki
Keyword(s):  
Periodic Acid ◽  
Interleukin 10 ◽  
Periodic Acid Schiff ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Infectious Dose ◽  
Inflammatory Protein ◽  
Mucosal Surfaces ◽  
Infected Urine ◽  
Mononuclear Cell Infiltrates

ABSTRACT Leptospirosis is potentially a fatal zoonosis acquired by contact of skin and mucosal surfaces with soil and water contaminated with infected urine. We analyzed the outcome of infection of C3H/HeJ mice with Leptospira interrogans serovar Copenhageni using an enzootic mode of transmission, the conjunctival route. Infection led to weight loss and L. interrogans dissemination from blood to urine, and spirochetes were detected in blood and urine simultaneously. The infectious dose that led to consistent dissemination to kidney after conjunctival infection was ∼108 leptospires. Interestingly, a lower number of spirochetes appeared to colonize the kidney, given that we quantified ∼105 and ∼10 leptospires per μl of urine and per μg of kidney, respectively. Leptospira-specific IgM and IgG were detected at 15 days postinfection, and isotyping of the Ig subclass showed that the total IgG response switched from an IgG1 response to an IgG3 response after infection with L. interrogans. Histological periodic acid-Schiff D staining of infected kidney showed interstitial nephritis, mononuclear cell infiltrates, and reduced size of glomeruli. Quantification of proinflammatory immunomediators in kidney showed that keratinocyte-derived chemokine, macrophage inflammatory protein 2, RANTES, tumor necrosis factor alpha, gamma interferon, and interleukin-10 were upregulated in infected mice. We show that the kinetics of disease progression after infection via the ocular conjunctiva is delayed compared with infection via the standard intraperitoneal route. Differences may be related to the number of L. interrogans spirochetes that succeed in overcoming the natural defenses of the ocular conjunctiva and transit through tissue.

scholarly journals Allergic Airway Disease Prevents Lethal Synergy of Influenza A Virus-Streptococcus pneumoniaeCoinfection

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Sean Roberts ◽  
Sharon L. Salmon ◽  
Donald J. Steiner ◽  
Clare M. Williams ◽  
Dennis W. Metzger ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Streptococcus Pneumoniae ◽  
Influenza Infection ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Bacterial Clearance ◽  
Content Type ◽  
Ifn Γ ◽  
The Impact ◽  
First Time

ABSTRACTFatal outcomes following influenza infection are often associated with secondary bacterial infections. Allergic airway disease (AAD) is known to influence severe complications from respiratory infections, and yet the mechanistic effect of AAD on influenza virus-Streptococcus pneumoniaecoinfection has not been investigated previously. We examined the impact of AAD on host susceptibility to viral-bacterial coinfections. We report that AAD improved survival during coinfection when viral-bacterial challenge occurred 1 week after AAD. Counterintuitively, mice with AAD had significantly deceased proinflammatory responses during infection. Specifically, both CD4+and CD8+T cell interferon gamma (IFN-γ) responses were suppressed following AAD. Resistance to coinfection was also associated with strong transforming growth factor β1 (TGF-β1) expression and increased bacterial clearance. Treatment of AAD mice with IFN-γ or genetic deletion of TGF-β receptor II expression reversed the protective effects of AAD. Using a novel triple-challenge model system, we show for the first time that AAD can provide protection against influenza virus-S. pneumoniaecoinfection through the production of TGF-β that suppresses the influenza virus-induced IFN-γ response, thereby preserving antibacterial immunity.IMPORTANCEAsthma has become one of the most common chronic diseases and has been identified as a risk factor for developing influenza. However, the impact of asthma on postinfluenza secondary bacterial infection is currently not known. Here, we developed a novel triple-challenge model of allergic airway disease, primary influenza infection, and secondaryStreptococcus pneumoniaeinfection to investigate the impact of asthma on susceptibility to viral-bacterial coinfections. We report for the first time that mice recovering from acute allergic airway disease are highly resistant to influenza-pneumococcal coinfection and that this resistance is due to inhibition of influenza virus-mediated impairment of bacterial clearance. Further characterization of allergic airway disease-associated resistance against postinfluenza secondary bacterial infection may aid in the development of prophylactic and/or therapeutic treatment against coinfection.

Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes

2007 ◽  
Vol 293 (3) ◽  
pp. L730-L739 ◽  
Author(s):  
Jill R. Johnson ◽  
Filip K. Swirski ◽  
Beata U. Gajewska ◽  
Ryan E. Wiley ◽  
Ramzi Fattouh ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inflammatory Responses ◽  
Airway Remodeling ◽  
Bronchial Hyperresponsiveness ◽  
Airway Disease ◽  
Allergic Airway Disease ◽  
Th Cell ◽  
And Function ◽  
Deficient Mice ◽  
Chronic Airway

Asthma is a chronic airway inflammatory disease that encompasses three cardinal processes: T helper (Th) cell type 2 (Th2)-polarized inflammation, bronchial hyperreactivity, and airway wall remodeling. However, the link between the immune-inflammatory phenotype and the structural-functional phenotype remains to be fully defined. The objective of these studies was to evaluate the relationship between the immunologic nature of chronic airway inflammation and the development of abnormal airway structure and function in a mouse model of chronic asthma. Using IL-4-competent and IL-4-deficient mice, we created divergent immune-inflammatory responses to chronic aeroallergen challenge. Immune-inflammatory, structural, and physiological parameters of chronic allergic airway disease were evaluated in both strains of mice. Although both strains developed airway inflammation, the profiles of the immune-inflammatory responses were markedly different: IL-4-competent mice elicited a Th2-polarized response and IL-4-deficient mice developed a Th1-polarized response. Importantly, this chronic Th1-polarized immune response was not associated with airway remodeling or bronchial hyperresponsiveness. Transient reconstitution of IL-4 in IL-4-deficient mice via an airway gene transfer approach led to partial Th2 repolarization and increased bronchial hyperresponsiveness, along with full reconstitution of airway remodeling. These data show that distinct structural-functional phenotypes associated with chronic airway inflammation are strictly dependent on the nature of the immune-inflammatory response.

scholarly journals Airway Remodeling Is Absent in CCR1−/− Mice During Chronic Fungal Allergic Airway Disease

2000 ◽  
Vol 165 (3) ◽  
pp. 1564-1572 ◽  
Author(s):  
Kate Blease ◽  
Borna Mehrad ◽  
Theodore J. Standiford ◽  
Nicholas W. Lukacs ◽  
Steven L. Kunkel ◽  
...  
Keyword(s):  
Airway Remodeling ◽  
Airway Disease ◽  
Allergic Airway Disease

scholarly journals Ability of Hydroxypropyl Chitosan Nail Lacquer To Protect against Dermatophyte Nail Infection

2014 ◽  
Vol 59 (4) ◽  
pp. 1844-1848 ◽  
Author(s):  
M. A. Ghannoum ◽  
L. Long ◽  
N. Isham ◽  
A. Bulgheroni ◽  
M. Setaro ◽  
...  
Keyword(s):  
Untreated Control ◽  
Periodic Acid ◽  
Control Sample ◽  
Trichophyton Mentagrophytes ◽  
Periodic Acid Schiff ◽  
Sample Mean ◽  
Content Type ◽  
Model Following ◽  
Nail Lacquer ◽  
Nail Infection

ABSTRACTThe development of a topical agent that would strengthen the nail, improve the natural barrier, and provide better drug penetration to the nail bed is needed. In this study, we examined the effects of a hydroxypropyl chitosan (HPCH)-based nail solution using a bovine hoof model. Following application of the nail solution, changes in the hardness of the hoof samples were measured using the Vickers method. Tensile and flexural strengths were tested by stretching or punching the samples, respectively. The ultrastructure was examined using scanning electron microscopy (SEM), and samples stained with periodic acid-Schiff (PAS) stain were used to determine the fungal penetration depth. The comparators included 40% urea and 70% isopropyl alcohol solutions. The HPCH nail solution increased hoof sample hardness in comparison to the untreated control sample (mean, 22.3 versus 19.4 Vickers pyramid number [HV]). Similarly, the HPCH solution increased the tensile strength (mean, 33.07 versus 28.42 MPa) and flexural strength (mean, 183.79 versus 181.20 MPa) compared to the untreated control. In contrast, the comparators had adverse effects on hardness and strength. SEM showed that the HPCH solution reduced the area of sample crumbling following abrasion compared to the untreated control (7,418 versus 17,843 pixels), and the PAS-stained images showed that the HPCH solution reduced penetration of the dermatophyte hyphae (e.g., penetration byTrichophyton mentagrophyteswas <25 μm at day 9 versus 275 μm in the untreated control). Unlike chemicals normally used in cosmetic treatments, repeated application of the HPCH nail solution may help prevent the establishment of new or recurring fungal nail infection.

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