Inhalation of Aspergillus fumigatus spores induces airway inflammation in mice in a similar manner as observed in Recurrent Airway Obstruction in horses

Morán, Gabriel; Ojeda, Gloria; Diedrichs, K; Ortloff, Alexander; Barría, Miguel; Folch, Hugo

doi:10.4067/s0301-732x2011000200009

Cited by 7 publications

(9 citation statements)

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“…Moreover, neutrophilic asthma is an important subgroup of the disease which includes patients with severe phenotypes. In the current study, the mice were exposed to fungus spores to generate a bronchial hypersensitivity response characterized by massive infiltration of the airways by inflammatory cells, as previously published [17,18].…”

Section: Discussionmentioning

confidence: 99%

“…Different groups of 5-month-old mice (eight mice per group) were housed in cages containing hay bedding that was contaminated with A. fumigatus and were kept in an isolation room for 16 days to allow for the induction of allergic airway inflammation, as described in previously published procedures [17,18]. After 16 days of exposure to this mold, the mice were placed in a remission environment for 10 days with the purpose of having the animals in a basal inflammatory condition before starting the antigenic challenge.…”

Section: Exposure Of Mice To a Fumigatus Sporesmentioning

confidence: 99%

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Immunobiology of S100A8 and S100A9 Proteins and Their Role in Acute Inflammation and Sepsis

Gazzar¹

2015

Int J Immunol Immunother

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Toll-like receptors (TLRs) constitute a protein family of cellular receptors that mediate the recognition of microbial challenges and the subsequent inflammatory response. The role of these receptors in allergic diseases of airways remains unclear. The objective of this study was to evaluate TLR2 and TLR4 expression in the lung in a murine model of bronchial hypersensitivity to Aspergillus fumigatus. Different groups of 5-month-old mice (Balb/c) were housed in cages containing hay bedding that was contaminated with A. fumigatus and were kept in an isolation room for 16 days to allow for the induction of allergic airway inflammation. The mice were then exposed once again to Aspergillus spores for 0, 2, 6, 12 and 24 hours; the mice were then sacrificed to obtain bronchoalveolar lavage fluid (BALF) or lung tissues for histology analysis; TLR2 and TLR4 expression. An unexposed group was used as a control. The results indicated that in this allergic mouse model, during the first hours of exposure to A. fumigatus spores in mice previously sensitized to this fungus, there is a decrease in the expression of TLR2 and TLR4 receptors with a concomitant increase in neutrophils in the BALF and histological changes associated with bronchial hyper responsiveness. The difference between our results and those of other studies could be due to the timing, dose, site and intensity of exposure of allergen, environmental factors and host genetic predisposition. This may explain the disparate results of TLR receptor expression during the development of allergies and airway inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Exposure Of Mice To a Fumigatus Sporesmentioning

confidence: 99%

Immunobiology of S100A8 and S100A9 Proteins and Their Role in Acute Inflammation and Sepsis

Gazzar¹

2015

Int J Immunol Immunother

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“…Fungus-contaminated hay was prepared as previously described by Morán et al 28 Contaminated hay was classified as previously described by Clarke and Madelin. 29 Animals were fed 300 g of grade III contaminated hay mixed with good quality hay, twice daily.…”

Section: Antigenic Preparations and Exposure To A Fumigatusmentioning

confidence: 99%

Tamoxifen as a new therapeutic tool for neutrophilic lung inflammation

et al. 2015

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Background and objective: Neutrophilic asthma is an important disease subgroup, including patients with severe phenotypes and erratic responses to standard treatments. Tamoxifen (TX), a selective estrogen receptor modulator (SERM) used as treatment of human breast cancer, has been shown to induce early apoptosis of equine blood and bronchoalveolar lavage fluid (BALF) neutrophils in vitro. Equine recurrent airway obstruction (RAO) is a naturally occurring neutrophilic condition, closely related with human asthma. Our purpose was to investigate the therapeutic potential of tamoxifen in horses with neutrophilic lung inflammation. Methods: Twelve horses underwent acute lung inflammation through exposure to allergens known to cause RAO, after which they received treatment with either tamoxifen or dexamethasone. Outcome measures included evaluation of clinical signs, BALF cytology, and early apoptosis of blood and BALF neutrophils. Results: Tamoxifen treatment decreased BALF neutrophil counts (65.3 ± 19.38% before treatment; 7.6 ± 4.5% 2 days post-treatment,; and 13.6 ± 9.3% 5 days post-treatment). A similar decrease was observed with dexamethasone treatment (48.6 ± 5.88% before treatment; 11.5 ± 8.1% 2 days post-treatment; 14.6 ± 10.3% 5 days post-treatment). Clinical and endoscopic scores improved in both treatment groups. Tamoxifen treatment significantly increased early apoptosis of peripheral blood neutrophils at 5 days post-treatment (27.04 ± 15.2%), and in BALF neutrophils at 2 and 5 days post-treatment (42.11 ± 11.67% and 48.98 ± 2.6%, respectively). Conclusion: Tamoxifen treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction in BALF neutrophils and improvement in the animals' clinical status.

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“…From their results, they concluded that CD4+, CD25+ cells present in the older mice, were less effective in suppressing the above-mentioned assays. These facts may explain why aging produces a progressive decline in immune regulation, and in the case of horses and in the mice of our experimental model [ 20 ], why age facilitates the occurrence of airway immune-mediated inflammation. On the other hand, our results indicate that upon stimulation only young mice show a significant increase of CD4+, CD25+, Foxp3+ cells percentage in the spleen, allowing us to propose that aging makes these cells less prone to proliferate or be recruited in response to antigenic challenge.…”

Section: Discussionmentioning

confidence: 99%

“…This increase occurs in parallel with airway inflammation, but, currently, we may only speculate about the importance of Treg in the control and resolution of the acute severe EA process. An approach to answer this question may be attempted through the use of a recently described murine EA model that we have set up in our laboratory [ 20 ]. The essence of this model is the use of hay contaminated with Aspergillus fumigatus as bedding for experimental mice.…”

Section: Introductionmentioning

confidence: 99%

Modulatory role of regulatory T cells in a murine model of severe equine asthma

et al. 2017

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BackgroundIt is accepted that T regulatory cells (Treg) control different types of immune responses. In connection with this role, we have recently described an important increase in CD4+, CD25high, Foxp3+ lymphocytes in the airway system of horses coursing with an exacerbation of severe equine asthma (EA). To explore the potential role of this population in the resolution of EA inflammation, we used a murine experimental model in which airway neutrophilic inflammation, which is similar to that observed in EA, is induced in mice by continual exposure to Aspergillus fumigatus contaminated hay. This model has the advantage that in mice we may induce a reduction of the Treg population using low doses of cyclophosphamide (Cy).ResultsThe results indicated that the percentage of Treg cells increased with allergen exposure, as in horses; and animals partially depleted of Treg cells by treatment with Cy showed increased airway inflammation, demonstrated by an increased percentage of neutrophils and specific immunoglobulins in bronchoalveolar lavage fluid (BALF). Furthermore, a histopathologic study of animals that were pretreated with Cy before antigenic challenge showed higher cellular infiltration in the lung and deeper remodeling changes in the bronchi, including epithelial and goblet cell hyperplasia as well as airway smooth muscle hypertrophy.ConclusionIn this murine model of EA, the reduced number and function of Treg induced by low doses of Cy, which directly correlates with increased airway inflammation and lung infiltration, indicates that Treg may play a major role in the regulation and resolution of EA.

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Inhalation of Aspergillus fumigatus spores induces airway inflammation in mice in a similar manner as observed in Recurrent Airway Obstruction in horses

Cited by 7 publications

References 50 publications

Immunobiology of S100A8 and S100A9 Proteins and Their Role in Acute Inflammation and Sepsis

Immunobiology of S100A8 and S100A9 Proteins and Their Role in Acute Inflammation and Sepsis

Tamoxifen as a new therapeutic tool for neutrophilic lung inflammation

Modulatory role of regulatory T cells in a murine model of severe equine asthma

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