Mouse model of Aspergillus and Alternaria induced rhinosinusitis

Ahn, Byung-Hoon; Park, Youn-Ho; Shin, Seung‐Heon

doi:10.1016/j.anl.2008.08.009

Cited by 16 publications

(18 citation statements)

References 18 publications

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“…Both Aspergillus and Alternaria spp. introduced repeatedly intranasally incite increased goblet cell hyperplasia, mucus production and enhanced IL-4 secretion consistent with Th2 cell-dependent sinus inflammation in mice 27,28 . Similarly, we have previously shown that hallmarks of asthma including airway hyperreactivity, airway eosinophil infiltration, and goblet cell metaplasia can be induced in mice challenged repeatedly intranasally with diverse fungi, including many of those identified in our patients 13,14 .…”

Section: Discussionmentioning

confidence: 64%

Airway surface mycosis in chronic TH2-associated airway disease

Porter

Lim

Maskatia

et al. 2014

Journal of Allergy and Clinical Immunology

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Background Environmental fungi have been linked to T helper type 2 (Th2) cell-related airway inflammation and the Th2-associated chronic airway diseases asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. Objective To determine the frequency of fungus isolation and fungus-specific immunity in Th2-associated and non-associated airway disease patients. Methods Sinus lavage fluid and blood were collected from sinus surgery patients (n=118) including CRS patients with and without nasal polyps and AFRS and non-CRS/non-asthmatic control patients. Asthma status was deteremined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. Peripheral blood mononuclear cells were restimulated with fungal antigens in an enzyme linked immunocell spot (ELISpot) assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared to fungus-specific IgE levels measured from plasma by ELISA. Results Filamentous fungi were significantly more commonly cultured from Th2-associated airway disease subjects (asthma, CRSwNP, or AFRS: n=68) compared to non-Th2-associated control patients (n=31); 74% vs 16% respectively, p<0.001. Both fungus-specific IL-4 ELISpot (n=48) and specific IgE (n=70) data correlated with Th2-associated diseases (sensitivity 73% and specificity 100% vs. 50% and 77%, respectively). Conclusions The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with Th2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients. Clinical Implications Airway fungi may contribute to the expression of sinusitis with nasal polyps and asthma, suggesting that efforts to eradicate fungi from the airways and environments of these patients should be considered.

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Section: Discussionmentioning

confidence: 64%

Airway surface mycosis in chronic TH2-associated airway disease

Porter

Lim

Maskatia

et al. 2014

Journal of Allergy and Clinical Immunology

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“…The murine model of CRS, initially described by Lindsay et al, 26 exhibits many of the same histologic changes seen in human CRS, including thickening of the lamina propria, mucosal inflammatory cell infiltrate, and increase in nonciliated epithelial cells with increased apocrine secretion. 27,28 Bony remodeling of the sinonasal cavity, including osteogenesis, osteitis, and periosteal fibrosis, has been described in several studies using a rabbit model of bacterial CRS. 7,[29][30][31] The underlying molecular mechanisms governing CRSassociated tissue remodeling, however, remain uncharacterized in animal models as well as in human subjects with CRS.…”

Section: T Is Widely Believed That Chronic Rhinosinusitis (Crs)mentioning

confidence: 99%

Altered expression of tissue remodeling genes in a mouse model of acute allergic rhinitis

Sautter

Delaney

Trune

2011

Int Forum Allergy Rhinol

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Background Osteogenesis, fibrosis and scarring are prominent pathologic changes resulting from chronic sinonasal inflammation, and these tissue changes may increase the degree of disease symptomatology and the level of surgical difficulty. Members of the Bone Morphogenetic Protein (BMP) and Fibroblast Growth Factor (FGF) families of cytokines and the Matrix Metalloproteinase (MMP) family of endopeptidases are known to regulate tissue remodeling in other disease processes, but their role in acute and chronic sinonasal inflammation remains undefined. Methods A previously described mouse model of acute allergic rhinitis secondary to Aspergillus fumigatis exposure in BALB/C mice was utilized. Intranasal challenge was performed one week following intraperitoneal sensitization with A. fumigatis extract and mice were sacrificed 6 hours (n=8) and 24 hours (n=8) later. Additional mice were intranasally challenged 3× per week and sacrificed at the end of 7 days (n=8) and 21 days (n=8). The snouts were processed for quantitative RT-PCR and compared to untreated controls for mRNA expression of BMP1, 2, 3, 4, 5, 6, 7, 8a, 8b, 9, 10, FGF1, 2, 3, 4, 5, 6, 7, 8, 10 and MMP1a, 2, 3, 7, 8, 9, 12 and 14. Additional 21 day mice were prepared for sinonasal histopathology. Control mice were treated with the same protocol, with intraperitoneal PBS and intranasal PBS substituted for A. fumigatis extract. Untreated mice were used for additional comparison. Results Compared to both the PBS and untreated control groups, statistically significant (p<0.05) up-regulation of MMP8 was observed in the 6 hour time point. Significant down-regulation of MMP8 was observed at 1 week. Significant up-regulation of FGF3 was observed at one week (p<0.05. BMP3 and BMP5 were significantly down-regulated in the 1 week group (p<0.05). The mice exhibited histologic sinonasal changes consistent with allergic inflammation. Conclusion Intranasal exposure to A. fumigatis results in altered expression of several tissue remodeling cytokines at varying time points in the acute allergic rhinitis mouse model. These changes in cytokine regulation may subsequently contribute to sinonasal osteogenesis, scarring and fibrosis as seen in chronic rhinosinusitis.

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“…Mice were also used to study viral, fungal, and allergic sinusitis. Ramadan et al and Ahn et al used intranasal inoculation with reoviruses or Aspergillus / Alternaria fungi to study the immune response to viruses and fungi, respectively . Lindsay et al developed a mouse model of chronic eosinophilic rhinosinusitis using Aspergillus fumigatus .…”

Section: Introductionmentioning

confidence: 99%

Models for the study of nasal and sinus physiology in health and disease: A review of the literature

Al-Sayed

Agu

Massoud

2017

Laryngoscope Investig Oto

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ObjectiveChronic sinusitis is a very common yet poorly understood medical condition with significant morbidity. Hence, it remains an entity that is difficult to treat with unsatisfactory outcomes of current management options. This necessitates research into the etiology and pathophysiology of the condition to enhance our knowledge and the therapeutic options. Unfortunately, this kind of research is not always feasible on human subjects due to practical and ethical limitations. Therefore, an alternative model that simulates the disease had to be found in order to overcome these limitations. These models could either be in vivo or in vitro. The aim of our review is to summarize the research findings and key discoveries of both in vivo and in vitro models of chronic sinusitis that have enhanced our understanding of the condition today and have paved the way for the future research of tomorrow. Data Sources: PubMed literature review.MethodsA review of the literature was conducted to identify the main successful in vivo and in vitro models for chronic sinusitis.ResultsCreating a successful model for chronic sinusitis is no easy task. Over the years, both in vivo animal models and in vitro tissue culture models were proposed, with each model having its accolades and pitfalls, with the ideal model remaining elusive to this day. However, advancing three‐dimensional cell culturing techniques seems to be a promising new way to find a more accurate model.ConclusionNone of the current models is perfect for a thorough study of chronic sinusitis. However, three‐dimensional cell cultures have the potential to bridge the gap between in vivo and in vitro studies.Level of EvidenceNA

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Mouse model of Aspergillus and Alternaria induced rhinosinusitis

Cited by 16 publications

References 18 publications

Airway surface mycosis in chronic TH2-associated airway disease

Airway surface mycosis in chronic TH2-associated airway disease

Altered expression of tissue remodeling genes in a mouse model of acute allergic rhinitis

Models for the study of nasal and sinus physiology in health and disease: A review of the literature

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