Elimination of Aspergillus fumigatus conidia from the airways of mice with allergic airway inflammation

Respiratory Research

Alexander M Sapozhnikov¹  Ekaterina A Servuli²  Elena L Bolkhovitina¹  Marina A Shevchenko¹ 

[1] Department of Immunology, Laboratory of Cell Interactions, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St. 16/10, 117997 Moscow, Russia;Faculty of Postgraduate Education, Pirogov Russian National Research Medical University, Ministry of Health, Ostrovitianov St. 1, 117997 Moscow, Russia

关键词: Confocal laser scanning microscopy;    Conducting airway;    Mucosal dendritic cells;    Neutrophils;    Aspergillus fumigatus;    Allergic airway inflammation;   

Others  :  793052
DOI  :  10.1186/1465-9921-14-78

 received in 2013-03-14, accepted in 2013-07-23,  发布年份 2013

【 摘 要 】

Background

Aspergillus fumigatus conidia can exacerbate asthma symptoms. Phagocytosis of conidia is a principal component of the host antifungal defense. We investigated whether allergic airway inflammation (AAI) affects the ability of phagocytic cells in the airways to internalize the resting fungal spores.

Methods

Using BALB/c mice with experimentally induced AAI, we tested the ability of neutrophils, macrophages, and dendritic cells to internalize A. fumigatus conidia at various anatomical locations. We used light microscopy and differential cell and conidium counts to determine the ingestion potential of neutrophils and macrophages present in bronchoalveolar lavage (BAL). To identify phagocyte-conidia interactions in conducting airways, conidia labeled with tetramethylrhodamine-(5-(and-6))-isothiocyanate were administered to the oropharyngeal cavity of mice. Confocal microscopy was used to quantify the ingestion potential of Ly-6G⁺ neutrophils and MHC II⁺ antigen-presenting cells located in the intraepithelial and subepithelial areas of conducting airways.

Results

Allergen challenge induced transient neutrophil recruitment to the airways. Application of A. fumigatus conidia at the acute phase of AAI provoked recurrent neutrophil infiltration, and consequently increased the number and the ingestion potential of the airway neutrophils. In the absence of recurrent allergen or conidia provocation, both the ingestion potential and the number of BAL neutrophils decreased. As a result, conidia were primarily internalized by alveolar macrophages in both AAI and control mice at 24 hours post-inhalation. Transient influx of neutrophils to conducting airways shortly after conidial application was observed in mice with AAI. In addition, the ingestion potential of conducting airway neutrophils in mice with induced asthma exceeded that of control mice. Although the number of neutrophils subsequently decreased, the ingestion capacity remained elevated in AAI mice, even at 24 hours post-conidia application.

Conclusions

Aspiration of allergen to sensitized mice enhanced the ingestion potential of conducting airway neutrophils. Such activation primes neutrophils so that they are sufficient to control dissemination of non-germinating A. fumigatus conidia. At the same time, it can be a reason for the development of sensitivity to fungi and subsequent asthma exacerbation.

【 授权许可】

   
2013 Shevchenko et al.; licensee BioMed Central Ltd.

【 图 表 】

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