Transcriptomic landscape of hepatic lymph nodes, peripheral blood lymphocytes and spleen of swamp buffaloes infected with the tropical liver fluke Fasciola gigantica

Abstract

The tropical liver fluke Fasciola gigantica is a parasitic helminth that has been frequently reported to infect mammals, typically involving water buffaloes. In this study, we characterized the tissue transcriptional landscape of buffaloes following infection by F. gigantica. RNAs were isolated from hepatic lymph nodes (hLNs), peripheral blood lymphocytes (pBLs), and spleen at 3-, 42- and 70-days post-infection (dpi), and all samples were subjected to RNA sequencing analyses. At 3 dpi, 2603, 460, and 162 differentially expressed transcripts (DETs) were detected in hLNs, pBLs, and spleen, respectively. At 42 dpi, 322, 937, and 196 DETs were detected in hLNs, pBLs, and spleen, respectively. At 70 dpi, 376, 334, and 165 DETs were detected in hLNs, pBLs, and spleen, respectively. Functional enrichment analysis identified upregulated immune-related pathways in the infected tissues involved in innate and adaptive immune responses, especially in hLNs at 42 and 70 dpi, and pBLs at 3 and 42 dpi. The upregulated transcripts in spleen were not enriched in any immune-related pathway. Co-expression network analysis further identified transcriptional changes associated with immune response to F. gigantica infection. Receiver operating characteristic (ROC) curve analysis showed that 107 genes in hLNs, 32 genes in pBLs, and 36 genes in spleen correlated with F. gigantica load. These findings provide new insight into molecular mechanisms and signaling pathways associated with F. gigantica infection in buffaloes. Author summary Fasciola gigantica is a socioeconomically important tropical liver fluke of mammals, causing fascioliasis–a neglected tropical disease. In the present study, RNA sequencing and bioinformatic approach were employed to explore the global transcriptional changes of hepatic lymph nodes (hLNs), peripheral blood lymphocytes (pBLs), and spleen of water buffaloes during F. gigantica infection at 3-, 42-, and 70-days post-infection (dpi). The results revealed significant transcriptional upregulation of genes associated with innate and adaptive immune responses in infected hLNs (42 and 70 dpi) and pBLs (3 and 42 dpi). However, downregulation of transcripts involved in immune response was detected in pBLs at 70 dpi. The downregulated transcripts were enriched in metabolic pathways, such as drug metabolism-cytochrome P450 in infected hLNs at 3 dpi. These findings provide new insight into the pathogenesis of F. gigantica in its natural mammalian host.