Role of NOD2 in regulating the immune response to Aspergillus fumigatus.

BACKGROUND: The nucleotide-binding oligomerization domain-2 (NOD2) is a type of intracellular receptor recognizing the cell wall molecules of bacteria and inducing the innate immune response. Its role in defense against fungal infection remains uncertain. We thus investigated the role of the NOD2/RIP2 pathway in host responses to Aspergillus fumigatus (Af) in RAW264.7 cells.
METHODS: RAW264.7 cells were cultured and Af conidia were added to stimulate the cells. The dynamic mRNA and protein expressions of NOD2 and RIP2 kinase were examined by real-time PCR and Western blotting. The protein expressions of nuclear factor-kappaB (NF-κB) and pro-inflammatory tumor necrosis factor-alpha and interleukin-8 were also investigated. Specific siRNA for NOD2 was synthesized and used to confirm the effect of NOD2 in the immune response to Af conidia.
RESULTS: The stimulation of the cell line by Af conidia resulted in a significantly increased expression of NOD2 protein and RIP2 kinase. The production of NF-κB and downstream cytokines were also increased simultaneously. On knockdown of the NOD2 using RNA interference, the activation of NF-κB was interrupted and the production of cytokines was reduced in the cell line stimulated by Af conidia.
CONCLUSION: These results suggested that Af conidia induced NF-κB activation in a NOD2-dependent manner, which potentially contributed to the innate immune response.