Decoding host immune response: circRNAs in Klebsiella variicola-infected chicken spleens

A newly discovered pathogen, Klebsiella variicola (K. variicola), poses a risk to food safety due to its zoonotic potential. Circular RNAs (circRNAs) are non-coding RNAs that have been shown to have important functions in the regulation of the host response to infection by a pathogen, but whether circRNAs participate in K. variicola infection and host response remains unclear. This study used high throughput sequencing to analyze the transcriptional profiles of host circRNAs in chicken spleens in response to K. variicola infection. A total of 53 circRNAs were significantly altered, including 22 upregulated and 31 downregulated circRNAs (p < 0.05). The biological function of the differentially expressed (DE) circRNAs was determined by Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses. It was found that the host genes of DE circRNAs were principally involved in the innate immune and inflammatory defense responses to the bacterium. Coupled with previous mRNA and microRNA sequencing data, a competing endogenous RNA analysis was performed and we first revealed two critical ceRNA axes, circRNA_4562/miR-3537/CARD11 and circRNA_0366/miR-129-5p/ITPR2, where circRNAs act as molecular sponges to relieve miRNA-mediated repression of CARD11 (caspase recruitment domain-containing protein 11) and ITPR2 (inositol 1,4,5-trisphosphate receptor type 2), activating innate immune signaling to combat infection. These findings broaden functional insights into circRNAs in bacterial-host interplay and establish novel molecular targets for deciphering avian immune defense against K. variicola, advancing ncRNA-based anti-infective strategies.