Nucleotide Oligomerization Domain 1 Ligation Suppressed Murine Allergen- Specific T-Cell Proliferation and Airway Hyperresponsiveness

作者：Tabeling Christoph; Scheer Heide; Schoenrock Stefanie M; Runge Franziska; Gutbier Birgitt; Lienau Jasmin; Hamelmann Eckard; Opitz Bastian; Suttorp Norbert; Mayer Konstantin; Behrens Georg M; Tschernig Thomas; Witzenrath Martin^*

来源：American Journal of Respiratory Cell and Molecular Biology, 2014, 50(5): 903-911.

DOI：10.1165/rcmb.2013-0333OC

• nucleotide oligomerization domain 1
• allergic airway inflammation
• airway hyperresponsiveness
• T-cell proliferation

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.

• 出版日期2014-5