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Intranasal CpG therapy attenuated experimental fungal asthma in a TLR9-dependent and -independent manner
Hemanth Ramaprakash1, Cory M Hogaboam
1Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
Background:
CpG administration abolishes airway inflammation and remodeling in acute models of allergic airway disease.
Methods:
Herein, we investigated the therapeutic effect of CpG in a chronic fungal model of asthma. TLR9+/+ and TLR9-/- mice were sensitized to soluble Aspergillus fumigatus antigens and challenged with live A. fumigatus conidia. Mice were treated with intraperitoneal (IP) or intranasal (IN) CpG, or left untreated 14-28 days after conidium challenge. All features of allergic airway disease were attenuated in TLR9+/+ mice treated with IN CpG, including airway hyperresponsiveness (AHR), mucus production, and peribronchial fibrosis.
Results:
TLR9-/- mice treated with IN CpG exhibited attenuated airway remodeling but not AHR. Whole-lung IL-12 levels were significantly elevated in both TLR9+/+ and TLR9-/- mice receiving IN CpG but not in either group receiving IP CpG. Whole-lung IL-10 levels were significantly elevated in IN CpG-treated TLR9+/+ mice but not in TLR9-/- mice receiving IN CpG. Increased whole-lung transcript and protein levels of the scavenger receptors SR-A and MARCO were observed in TLR9-/- mice compared with TLR9+/+ mice, possibly accounting for the CpG responsiveness in the knockout group.
Conclusions:
Together, these data show that IN CpG has a therapeutic effect during established fungal asthma, which is TLR9 dependent and independent.
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