Alternaria alternata allergens: Markers of exposure, phylogeny and risk of fungi-induced respiratory allergy

Gabriel, Marta Fonseca; Postigo, Idoia; Tomaz, Cândida T.; Martı́nez, Jorge

doi:10.1016/j.envint.2016.01.003

Cited by 127 publications

(102 citation statements)

References 116 publications

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“…As shown in Figure 8A to elicit allergic lung disease. [41][42][43] Here, we show that repetitive stimulation with this filtrate in volumes that are limited to the nasal cavity 19,22 results in prominent eosinophilic inflammation within the nasal mucosa. Eosinophil recruitment is absent in Rag1 À/À mice, suggesting a critical role for Th2 lymphocytes.…”

Section: Rhinitis Followed By Virus Infection Results In An Increasmentioning

confidence: 60%

“…In this study, our primary goal was to examine eosinophil‐mediated responses to influenza virus infection in the upper airways. Towards this end, we have adapted a strategy of repetitive dosing with a filtrate of the saprophytic fungus, A. alternata , used in earlier studies to elicit allergic lung disease . Here, we show that repetitive stimulation with this filtrate in volumes that are limited to the nasal cavity results in prominent eosinophilic inflammation within the nasal mucosa.…”

Section: Discussionmentioning

confidence: 84%

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Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection

Redes

Percopo

et al. 2018

Clin Experimental Allergy

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Repetitive administration of A. alternata resulted in inflammation of the nasal mucosae and unanticipated morbidity and mortality in response to subsequent challenge with influenza virus. Interestingly, and in contrast to findings in the lower airways, eosinophils recruited to the nasal passages provided no protection against lethal infection. As increased susceptibility to influenza virus among individuals with rhinitis has been the subject of several clinical reports, this model may be used for further exploration of these observations.

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Section: Rhinitis Followed By Virus Infection Results In An Increasmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 84%

Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection

Redes

Percopo

et al. 2018

Clin Experimental Allergy

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“…For reasons that are not fully understood, repetitive sensitization to A. alternata is among the major risk factors for developing asthma and other allergic manifestations . Sixteen independent A. alternata allergens have been identified, at least nine of which share cross‐reactive epitopes with allergens from other fungal species …”

Section: Introductionmentioning

confidence: 99%

“…16 Sixteen independent A. alternata allergens have been identified, at least nine of which share crossreactive epitopes with allergens from other fungal species. 16,17 Several distinct mouse models of allergic airways inflammation have been developed featuring A. alternata spores and filtrates. 18,19 Among recent findings, Kim and colleagues 20 found that a single intranasal inoculum of A. alternata amplified eosinophil recruitment secondary to primary sensitization to ryegrass antigens.…”

Section: Introductionmentioning

confidence: 99%

Eosinophil persistence in vivo and sustained viability ex vivo in response to respiratory challenge with fungal allergens

Geslewitz

Percopo

Rosenberg

2017

Clin Experimental Allergy

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Summary Background Eosinophils are immunomodulatory leucocytes that contribute to the pathogenesis of Th2‐driven asthma and allergic lung diseases. Objective Our goal was to identify unique properties of eosinophils recruited to the lungs and airways of mice in response to challenge with asthma‐associated fungal allergens. Methods Mice were challenged intranasally on days 0, 3 and 6 with a filtrate of Alternaria alternata. Recruited eosinophils were enumerated in bronchoalveolar lavage fluid. Eosinophils were also isolated from lungs of mice sensitized and challenged with Aspergillus fumigatus and evaluated ex vivo in tissue culture. Results Eosinophils persist in the airways for several weeks in response to brief provocation with A. alternata in wild‐type, Gm‐csf‐ and eotaxin‐1‐gene‐deleted mice, while eosinophils are recruited but do not persist in the absence of IL‐13. Eosinophils isolated from the lungs A. alternata‐challenged mice are cytokine‐enriched compared to those from IL5tg mice, including 800‐fold higher levels of eotaxin‐1. Furthermore, eosinophils from the lungs and spleen of fungal allergen–challenged wild‐type mice are capable of prolonged survival ex vivo, in contrast to eosinophils from both untreated and fungal allergen–challenged IL5tg mice, which undergo rapid demise in the absence of exogenous cytokine support. TNF‐α (but not IL5, IL‐3, eotaxin‐1 or GM‐CSF) was detected in supernatants of ex vivo eosinophil cultures from the lungs of fungal allergen–challenged wild‐type mice. However, neither TNF‐α gene deletion nor anti‐TNF‐α neutralizing antibodies had any impact sustained eosinophil survival ex vivo. Conclusion and Clinical Relevance Eosinophils are phenotypically and functionally heterogeneous. As shown here, eosinophils from fungal allergen–challenged wild‐type mice maintain a distinct cytokine profile, and, unlike eosinophils isolated from IL5tg mice, they survive ex vivo in the absence of exogenous pro‐survival cytokine support. As treatments for asthma currently in development focus on limiting eosinophil viability via strategic cytokine blockade, the molecular mechanisms underlying differential survival merit further investigation.

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“…The fungus Alternaria alternata is a common allergen, widespread in many indoor and outdoor habitats, found to thrive on various types of vegetation. Contact with this fungus is unavoidable, given that Alternaria produces thousands of spores per cubic meter of air 21,22 . Alternaria poses a general health threat as one of the most abundant sources of aeroallergens known to trigger immune sensitization and as a primary risk factor for the development of asthma.…”

Section: Fungal Extract Solutionmentioning

confidence: 99%

Establishment and Characterization of a Multi-Purpose Large Animal Exposure Chamber for Investigating Health Effects

Peng

Maltz

et al. 2018

Preprint

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Air pollution poses a significant threat to the environment and human health. Most in-vivo health studies conducted regarding air pollutants, including particulate matter (PM) and gas phase pollutants, have been either through traditional medical intranasal treatment or using a tiny chamber, which limit animal activities. In this study, we designed and tested a large, whole-body, multiple animal exposure chamber with uniform dispersion and exposure stability for animal studies. The chamber simultaneously controls particle size distribution and PM mass concentration. Two different methods were used to generate aerosol suspension through either soluble material (Alternaria extract), liquid particle suspension (Nanosilica solution) or dry powder (silica powder). We demonstrate that the chamber system provides well controlled and characterized whole animal exposures, where dosage is by inhalation of particulate matter.

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Alternaria alternata allergens: Markers of exposure, phylogeny and risk of fungi-induced respiratory allergy

Cited by 127 publications

References 116 publications

Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection

Alternaria alternata challenge at the nasal mucosa results in eosinophilic inflammation and increased susceptibility to influenza virus infection

Eosinophil persistence in vivo and sustained viability ex vivo in response to respiratory challenge with fungal allergens

Establishment and Characterization of a Multi-Purpose Large Animal Exposure Chamber for Investigating Health Effects

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