Role of NODs and their signaling pathways in invasive pulmonary aspergillosis

Abstract:

[Objective] To study the role of the nucleotide binding oligomerization domain-like receptor (NODs) and their signaling pathways in the pathogenesis of invasive pulmonary aspergillosis (IPA) in mice. [Methods] Mice were randomly divided into three groups: negative control, mice infected with Aspergillus fumigatus only and mice of combination of immunosuppression and Aspergillus fumigatusinfection (IPA group). Only IPA mice were immunosuppressed with Cyclophosphamide (100 mg/d) for 2 d before Aspergillus fumigatus spores were inhaled into mice of different groups, normal saline was used instead for negative control. Then mice were killed at different time points and lung tissues were collected for biopsy and Aspergillus fumigatus colony count. RT-PCR and Western blot were used to measure NOD1, NOD2, RIP2 mRNA level and TNF-α protein expression in lung tissues, respectively. [Results] At 72 h of post-infection, severe inflammation and a large number of hyphae were observed in lung tissues of IPA mice. Their Aspergillus fumigatus load at all time points were higher when compared with mice infected with Aspergillus fumigatus only, and their NOD1 and RIP2 mRNA levels were continuously lower. While NOD2 mRNA was abnormally highly expressed at 24 h and stayed at low expression level afterwards. TNF-α was highly expressed in mice infected with Aspergillus fumigatus only and reached the peak at 48 h and 72 h post-transfection. However, TNF- α was released slowly and lowly in IPA mice. [Conclusion] Persistently inhibited NOD1 and RIP2 expression along with late-stage inhibited NOD2 expression in IPA mice resulted in the low-expression of proinflammatory cytokine, which may led to the development of invasive pulmonary aspergillosis.