The cytosolic
nucleotide oligomerization domain (
NOD)-like receptors NOD1 and NOD2 are important contributors to the intracellular recognition of pathogens including Chlamydophila pneumoniae, but little is known about their influence on
allergen-induced airway
inflammation. In BALB/c mice, we observed that
infection with C. pneumoniae before systemic sensitization with
ovalbumin (OVA) and local OVA airway exposure diminished
airway hyperresponsiveness (AHR). Thus, the impact of the NOD1 agonist FK156 and the NOD2 agonist
muramyl dipeptide given 6 hours before each sensitization or airway challenge was evaluated regarding AHR, OVA-specific plasma
immunoglobulins, bronchoalveolar lavage fluid differentials, and
cytokines. Spleen dendritic cells of FK156-treated mice were isolated and cocultured with OVA-specific T cells isolated from DO11.10 mice, and T-cell proliferation was quantified after OVA restimulation. T-cell proliferation was investigated in vivo in lungs and lymph nodes of FK156-treated and OVA-exposed DO11.10 mice. FK156, but not
muramyl dipeptide, reduced AHR and pulmonary eosinophilic infiltration if given before OVA sensitization or challenge, whereas T-helper (Th)2
cytokines were not diminished. Dendritic cells from FK156-treated mice evoked less OVA-specific T-cell proliferation as compared with
solvent-treated controls. Similarly,
antigen-specific T-cell activation in lung tissue was diminished after FK156 treatment. We conclude that NOD1 activation reduced AHR in
allergen-induced
lung inflammation, which was accompanied by a reduction of
allergen-specific T-cell proliferation.