Respiratory tract allergic disease and atopy: experimental evidence for a fungal infectious etiology.
Allergic asthma is an obstructive lung disease linked to environmental exposures that elicit allergic airway inflammation and characteristic antigen-specific immunoglobulin reactions termed atopy. Analyses of asthma pathogenesis using experimental models have shown that T helper cells, especially T helper type 2 (Th2) cells and Th2 cytokines such as interleukin 4 (IL-4) and IL-13, are critical mediators of airway obstruction following allergen challenge, but the environmental initiators of lung Th2 responses are less defined. Our studies demonstrate that fungal-derived proteinases that are commonly found in home environments are requisite immune adjuvants capable of eliciting robust Th2 responses and allergic lung disease in mice. We have further shown that common household fungi readily infect the mouse respiratory tract and induce both asthma-like disease and atopy to otherwise innocuous bystander antigens through the secretion of proteinases. These findings support the possibility that asthma and atopy represent a reaction to respiratory tract fungal infection, suggesting novel means for diagnosis and therapy of diverse allergic disorders.
Porter
Paul
P
Departments of Medicine, Pathology and Immunology, and Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Polikepahad
Sumanth
S
Qian
Yuping
Y
Knight
J Morgan
JM
Lu
Wen
W
Tai
Wendy M-T
WM
Roberts
Luz
L
Ongeri
Valentine
V
Yang
Tianshu
T
Seryshev
Alexander
A
Abramson
Stuart
S
Delclos
George L
GL
Kheradmand
Farrah
F
Corry
David B
DB
D000276:Adjuvants, Immunologic; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000382:microbiology*; D004195:Disease Models, Animal; D005656:Fungal Proteins / Q000009:adverse effects / Q000276:immunology; D005658:Fungi / Q000201:enzymology* / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D009181:Mycoses / Q000276:immunology / Q000382:microbiology*; D010447:Peptide Hydrolases / Q000009:adverse effects / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology / Q000382:microbiology*; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000485:Allergens; D005656:Fungal Proteins; D018793:Interleukin-13; D015847:Interleukin-4; D010447:Peptide Hydrolases
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