Changes of nucleotide-binding oligomerization domains (NODs) signaling pathway in the incidence and development of invasive pulmonary aspergillosis

This study investigates the effect of nucleotide-binding oligomerization domains (NODs) signal pathway in invasive pulmonary aspergillosis. Mice were randomly divided into three groups: 1) normal mice (control group), 2) normal mice infected with Aspergillus fumigates, 3) normal mice treated with immunosuppressant and inoculated with A. fumigatus (IPA Model). Mice were sacrificed at different time points after inhaling A. fumigatus spores by nose. Their lungs were extracted under sterile condition, and were used to count the fungal colonies; and also the pathological sections of lungs were observed by HE staining. RT-PCR was used to detect the expression of the NOD1, NOD2 and RIP2 mRNA of mice lung. Western blot was used to detect the expression of TNF-α. 72 h after inhaling A. fumigatus spores, a large number of hyphae and severe inflammation were found in the lung of IPA model mice group; and the lung burden of IPA mice were more than that of normal+A. fumigatus group at each time points. When compared with normal+A. fumigatus group, the expressions of NOD1 and RIP2 mRNA were persistently descending in IPA model mice group; the expression of NOD2 mRNA was abnormally raised in early stage of infection (24 h), then decreased in the later stage. However, in normal+A. fumigatus group, proinflammatory cytokine TNF-α exhibited high expression at the early stages of infection, and the highest expression levels appeared at 48 or 72 h, then decreased and returned to normal level. In the group of the IPA mouse, proinflammatory cytokines TNF-α were released at slow and low level. Persistently low expression of NOD1 and RIP2, was seen in early excessive activation. Key words: Invasive pulmonary aspergillosis (IPA), nucleotide-binding oligomerization domains (NODs), RIP2, pathogenesis.