Aspergillus fumigatus synergistically enhances mite-induced allergic airway inflammation.
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.


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.
Fukushima
Chizu
C
2nd Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Matsuse
Hiroto
H
Fukahori
Susumu
S
Tsuchida
Tomoko
T
Kawano
Tetsuya
T
Senjyu
Hideaki
H
Kohno
Shigeru
S
D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D001249:Asthma / Q000150:complications* / Q000276:immunology / Q000382:microbiology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008925:Mites / Q000276:immunology*; D055271:Mucin 5AC / Q000378:metabolism; D011014:Pneumonia / Q000150:complications* / Q000276:immunology / Q000382:microbiology*
D016207:Cytokines; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC