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25 June 2010

Aspergillus fumigatus synergistically enhances mite-induced allergic airway inflammation

Chizu FukushimaABCE, Hiroto MatsuseACD, Susumu FukahoriBDF, Tomoko TsuchidaBDF, Tetsuya KawanoEF, Hideaki SenjyuDF, Shigeru KohnoDF

Med Sci Monit 2010; 16(7): BR197-202 :: ID: 880920

Abstract

Background: Infection is an important trigger of exacerbation of bronchial asthma. The fact that Aspergillus fumigatus (Af) causes a distinct clinical syndrome, allergic bronchopulmonary aspergillosis (ABPA), suggests unique immunological properties in allergic asthma. The present study aimed to determine how Af enhances preexisting allergic airway inflammation and colonizes the airway in asthma.
Material/Methods: Six groups of BALB/c mice were prepared: Control; live or dead Af-infected (Live Af or Dead Af); Dermatophagoides farinae (Df) allergen-sensitized (Df); and Df-sensitized plus live or dead Af-infected (Df-live Af or Df-dead Af). Pulmonary pathology, cytokine profiles and mucous production in the airway were evaluated in these groups.
Results: Af infection significantly enhanced Df allergen-induced eosinophilic inflammation via enhancement of Th2-like response. Live, but not dead, Af significantly exacerbated neutrophilic inflammation. Induction of IL-13 and Muc5ac proteins by Df allergen sensitization was significantly enhanced by both live and dead Af infection, resulting in mucous hypersecretion.
Conclusions: Collectively, the present study showed that mite allergen sensitization concomitant with Af infection enhanced Th2-dominant immune response in the airway, which induced mucous hypersecretion and potentially permitted further colonization by Af spores. It is likely that Af enhances allergic airway inflammation as an allergen, while it enhances neutrophilic airway inflammation as a pathogen. Future studies on pharmacological intervention in the present murine model utilizing glucocorticoid, and anti-fungal drugs are thus promising.

Keywords: Lung - pathology, Mice, Inbred BALB C, Cytokines - metabolism, Cell Count, Bronchoalveolar Lavage Fluid - cytology, Asthma - microbiology, Aspergillus fumigatus - immunology, Mites - immunology, Mucin 5AC - secretion, Pneumonia - microbiology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750