Mannose-binding lectin deficiency alters the development of fungal asthma: effects on airway response, inflammation, and cytokine profile.
Aspergillus fumigatus is a major fungal pathogen that may be fatal to immunocompromised individuals and causes airway hyperreactivity and remodeling in sensitized individuals. Herein, we examined the role of mannose-binding lectin (MBL), a complement-activating plasma protein, during pulmonary innate and allergic immune responses directed against A. fumigatus spores or conidia. Neither group of nonsensitized MBL-A-sufficient (MBL-A+/+) nor -deficient (MBL-A-/-) mice challenged with an intravenous or intratracheal (i.t.) bolus of A. fumigatus spores experienced fungus-induced mortality, but marked airway remodeling was observed in MBL-A-/- mice challenged i.t. with conidia. In a model of chronic fungal asthma, MBL-A+/+ and MBL-A-/- A. fumigatus-sensitized mice were examined at days 4 and 28 after an i.t. challenge with A. fumigatus conidia. Airway hyperresponsiveness in sensitized MBL-A-/- mice was significantly decreased at both times after conidia challenge compared with the sensitized MBL-A+/+ group. In the sensitized MBL-A-/- mice, whole lung T helper cell type 2 cytokine levels were significantly decreased at day 4 after conidia, and whole lung interferon-gamma levels were significantly increased at day 28 after conidia when compared with controls. However, histological evidence showed similar airway remodeling at day 28 after conidia (i.e., subepithelial fibrosis and goblet cell metaplasia) in the two groups of mice. Thus, these findings show that MBL-A is not required for mouse survival following exposure to A. fumigatus conidia, and this murine collectin isoform contributes to the development and maintenance of airway hyperresponsiveness but not chronic airway remodeling during chronic fungal asthma.
Hogaboam
Cory M
CM
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Takahashi
Kazue
K
Ezekowitz
R Alan B
RA
Kunkel
Steven L
SL
Schuh
Jane M
JM
D000403:Airway Resistance / Q000276:immunology*; D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology; D001249:Asthma / Q000382:microbiology* / Q000503:physiopathology; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009181:Mycoses / Q000382:microbiology / Q000503:physiopathology*; D015996:Survival Rate
D016207:Cytokines; D037601:Mannose-Binding Lectin