Nucleotide-binding oligomerization domain2 (NOD2) of the NOD-like receptors (NLRs) and Toll-like receptor4 (TLR4) of the TLRs are major pattern-recognition receptors. They sense different microbial pathogens and play important roles in innate immunity. Current in vivo and in vitro studies have shown that TLR4 and NOD2 act in anti-Aspergillus fumigatus infection. Herein, the cross-interaction between membrane-bound TLR4 and cytosolic NOD2 was investigated using murine RAW264.7 macrophages as a cell model. The expression of the TLR4 and NOD2 genes was significantly stimulated by A. fumigatus conidia. Macrophages defended against A. fumigatus conidia invasion by releasing the inflammatory cytokine tumor necrosis factor (TNF)-α. TLR4 silencing was found to lead to a decrease in the expression of NOD2 and inflammatory response in RAW264.7 macrophages by A. fumigatus conidia stimulation. This demonstrated that silencing TLR4 could down-regulate NOD2-mediated inflammatory response in macrophages through the stimulation of A. fumigatus conidia. Therefore, it is proposed that TLR4 might play a more important role than NOD2 in defense against A. fumigatus conidia invasion. Elucidating the molecular mechanism underlying this process requires further investigation.

Keywords: : Aspergillus fumigatus conidia, macrophages, Toll-like receptor4 (TLR4), nucleotide-binding oligomerization domain2 (NOD2), innate immunity.