title: Role of NOD2 in regulating the immune response to Aspergillus fumigatus.
abstract: 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.
  
  
  CONCLUSIONS
  These results suggested that Af conidia induced NF-κB activation in a NOD2-dependent manner, which potentially contributed to the innate immune response.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, 200032, Shanghai, China.
authors.forename: Zhuo-zhe
authors.initials: ZZ
authors.lastname: Li
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Tao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Hui-jun
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Jie-Ming
authors.initials: JM
authors.lastname: Qu
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000502:physiology*; D002460:Cell Line; D016209:Interleukin-8 / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology*; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D013172:Spores, Fungal / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse