The ovalbumin (OVA)-alum mouse model, which induces a Th2-biased immune response, is commonly used to study allergic airway inflammation. However, the artificial nature of this model limits its relevance to environmental or infection-related airway diseases. The free-living environmental protozoan Acanthamoeba is a potential trigger of airway inflammation, but its immune mechanisms remain largely unknown. To compare these 2 models of airway inflammation, this study carried out microarray-based transcriptomic analysis of lung tissue obtained from mice with OVA-alum treatment or intranasal Acanthamoeba exposure. Compared to controls, OVA-alum treatment induced broad transcriptional changes involving >2,900 probes (fold change ≥1.5); Acanthamoeba exposure led to a substantially weaker response, with <500 probes affected at the same threshold. Unlike the OVA-alum–treated group, the Acanthamoeba-exposed mice showed minimal overlap with only 5 genes significantly downregulated, suggesting a distinct immune activation profile. Downregulation of genes related to the immunoglobulin variable region (Ighv1-58 and Igkv3-10) and eosinophil function (Rnase2a) in the Acanthamoeba group suggest suppression of a typical Th2/humoral response. Heatmap and clustering analysis demonstrated clear separation between the Acanthamoeba, OVA-alum, and control groups. Taken together, these results suggest that Acanthamoeba induces a unique airway immune response that is markedly different from traditional Th2-dominant inflammation, and may be a more suitable model for studying environmentally-induced or infection-related respiratory diseases.
Clonorchis sinensis is a food-borne trematode that infects more than 15 million people. The liver fluke causes clonorchiasis and chronical cholangitis, and promotes cholangiocarcinoma. The underlying molecular pathogenesis occurring in the bile duct by the infection is little known. In this study, transcriptome profile in the bile ducts infected with C. sinensis were analyzed using microarray methods. Differentially expressed genes (DEGs) were 1,563 and 1,457 at 2 and 4 weeks after infection. Majority of the DEGs were temporally dysregulated at 2 weeks, but 519 DEGs showed monotonically changing expression patterns that formed seven distinct expression profiles. Protein-protein interaction (PPI) analysis of the DEG products revealed 5 sub-networks and 10 key hub proteins while weighted co-expression network analysis (WGCNA)-derived gene-gene interaction exhibited 16 co-expression modules and 13 key hub genes. The DEGs were significantly enriched in 16 Kyoto Encyclopedia of Genes and Genomes pathways, which were related to original systems, cellular process, environmental information processing, and human diseases. This study uncovered a global picture of gene expression profiles in the bile ducts infected with C. sinensis, and provided a set of potent predictive biomarkers for early diagnosis of clonorchiasis.
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