IL-18 modulates chronic fungal asthma in a murine model; putative involvement of Toll-like receptor-2.
Fungus-induced asthmatic disease is characterized by persistent airway hyperreactivity and remodeling.


OBJECTIVE
To determine the role of IL-18 in the allergic airway response to Aspergillus fumigatus conidia in a murine model of A. fumigatus-induced asthma.


METHODS
A. fumigatus-sensitized mice were depleted of IL-18 using a polyclonal anti-IL-18 antibody for 3 days after a conidia challenge.


RESULTS
Airway hyperresponsiveness and eosinophil numbers were significantly elevated 3-30 days after conidia challenge compared to the normal serum-treated group. Histological evidence showed retention of A. fumigatus conidia, airway remodeling, subepithelial fibrosis, and increased collagen deposition in the lungs of IL-18-depleted mice at day 30 after the conidia challenge. Prolonged retention of conidia in IL-18 depleted A. fumigatus-sensitized mice was associated with decreased Toll-like receptor-2 (TLR-2) expression compared with the control group.


CONCLUSIONS
IL-18 modulates the innate immune response against A. fumigatus conidia and prevents the development of severe fungus-induced asthmatic disease.
Blease
K
K
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
Kunkel
S L
SL
Hogaboam
C M
CM
D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000302:isolation & purification; D001249:Asthma / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000209:etiology; D054413:Chemokine CCL11; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis; D019742:Chemokines, CC / Q000096:biosynthesis; D002908:Chronic Disease; D029721:Drosophila Proteins; D004804:Eosinophils / Q000502:physiology; D005260:Female; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D020382:Interleukin-18 / Q000032:analysis / Q000502:physiology*; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D009504:Neutrophils / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D054426:Chemokine CXCL2; D018925:Chemokines; D019742:Chemokines, CC; C404915:Cxcl2 protein, mouse; D029721:Drosophila Proteins; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma