511 Role of NLR (Nucleotide Oligomerization Domain (NOD)—like Receptor) on Allergic Inflammation in a Mouse Model of Allergic Rhinitis

Abstract

BackgroundRecently, a new set of pattern-recognition receptors, the nucleotidebinding oligomerization domain (Nod)-like receptors (NLRs), have emerged. Their activation, either by allergens or microbes, triggers an inflammatory response. Objective: To investigate whether recognition of bacterial microbial-associated molecular patterns in the nose may result in susceptibility to developing allergic reactions, and to understand the molecular mechanisms by which such triggers block natural tolerance.MethodsLigands of intracellular microbial-associated molecular pattern recognition receptors—the nucleotidebinding oligomerization domain (Nod)-like receptors, Nod1 and Nod2—were given intranasally with antigen, and their ability to modulate airway tolerance was analyzed. Seventy 2 mice were randomized to one of 6 groups: control (n = 12), AR (n = 12), pre NOD1 group (n = 12), pre NOD2 group (n = 12), post NOD1 group (n = 12), and post NOD2 group (n = 12). All mice except for the control group were sensitized by an intraperitoneal injection of ovalbumine (OVA) and aluminum hydroxide. Two weeks after sensitization, all sensitized mice were challenged intranasally with OVA. The control group was received phosphate buffered saline intranasally. The allergic symptom after the final challenge was recorded. Interleukin (IL)-5, interferon-γ (IFN- γ), and IL-10 levels in nasal lavage fluid (NALF), as well as serum OVA-specific IgE levels were measured. The number of eosinophils in lamina propria was evaluated. The levels of T-bet, GATA-3, and Foxp3 mRNA expression in splenic mononuclear cells were determined by real-time polymerase chain reaction.Results & ConclusionWe show that a Nod-like receptor is a novel, previously unrecognized, pathway that adversely links innate and adaptive immunity and leads to allergic rhinitis.