Avian pathogenic E. coli (APEC), one of the widespread zoonotic-pathogen, can cause a series of diseases collectively known as colibacillosis. This disease can cause thousands of million dollars economic loss each year in poultry industry and threaten to human health via meat or egg contamination. However, the detailed molecular mechanism underlying APEC infection is still not fully understood. Circular RNAs, a new type of endogenous noncoding RNA, have been demonstrated to involve in various biological processes. However, it is still not clear whether the circRNAs participate in host response against APEC infection. Herein, we utilized the high-throughput sequence technology to identify the circRNA expression profiles in APEC infected HD cells. A total of di erentially expressed (DE) circRNAs were detected in the comparison of APEC infected HD cells vs. wild type HD cells, which were involved in MAPK signaling pathway, Endocytosis, Focal adhesion, mTOR signaling pathway, and VEGF signaling pathway. Specifically, the source genes (BRAF, PPP CB, BCL L , RAB A, and TSC ) and their corresponding DE circRNAs may play a significant role in APEC infection. Moreover, based on ceRNA regulation, we constructed the circRNA-miRNA network and identified a couple of important regulatory relationship pairs related to APEC infection, including circRAB A-gga-miR-b-p, circRAB A-gga-miR-, and circTSC -gga-miR--p. Results indicate that the aforementioned specific circRNAs and circRNA-miRNA network might have important role in regulating host immune response against APEC infection. This study is the first time to investigate the circRNAs expression profile and the biological function of the source genes of the identified DE circRNAs after APEC infection of chicken HD cells. These results would contribute to a better understanding of the molecular mechanisms in host response against APEC infection.
Colibacillosis is an acute and chronic avian disease caused by avian pathogenic E. coli (APEC). Previous studies have demonstrated that RIP2 plays a significant role in APEC infection. Moreover, increasing evidence indicates that microRNAs (miRNAs) are involved in host–pathogen interactions and the immune response. However, the role of miRNAs in the host against APEC infection remains unclear. Herein, we attempted to reveal new miRNAs potentially involved in the regulation of the immune and inflammatory response against APEC infection, with a particular focus on those possibly correlated with RIP2 expression, via miRNA-seq, RT-qPCR, Western blotting, dual-luciferase reporter assay, and CCK-8. The results showed that a total of 93 and 148 differentially expressed (DE) miRNAs were identified in the knockdown of RIP2 cells following APEC infection (shRIP2+APEC) vs. knockdown of RIP2 cells (shRIP2) and shRIP2 vs. wild-type cells (WT), respectively. Among those identified DE miRNAs, the biological function of gga-miR-455-5p was investigated. It was found that gga-miR-455-5p regulated by RIP2 was involved in the immune and inflammatory response against APEC infection via targeting of IRF2 to modulate the expression of type I interferons. Additionally, RIP2 could directly regulate the production of the type I interferons. Altogether, these findings highlighted the crucial role of miRNAs, especially gga-miR-455-5p, in host defense against APEC infection.
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