CRISPR/Cas9‐mediated gene knockout of Sj16 in Schistosoma japonicum eggs upregulates the host‐to‐egg immune response

Abstract

Schistosomiasis is an important, neglected tropical disease. Schistosoma japonicum can evade host attacks by regulating the host's immunity, causing continuous infection. However, interactions between the host's immune system and S. japonicum are unclear. Our previous research found that the Sj16 protein isolated from S. japonicum has an anti-inflammatory effect in the host. However, the role of Sj16 in the regulation of host immunity in S. japonicum infection is not clear.Here, we applied the CRISPR/Cas9 technique to knockout Sj16 in S. japonicum eggs and investigated the effect of Sj16 in regulating host immunity. We found egg viability decreased after Sj16 knockout. In addition, we found granulomatous inflammation increased, the T-cell immune response enhanced and the immune microenvironment changed in mice model injected with Sj16-knockout eggs by tail vein. These findings suggested that S. japonicum could regulate host immunity through Sj16 to evade the host immune attack and cause continuous infection. In addition, we confirmed the application of CRISPR/Cas9-mediated gene reprogramming for functional genomics in S. japonicum.

Schistosome Transgenesis: The Long Road to Success

“…Inflammatory responses were more severe after injecting Sj16 knockdown eggs, concurrent with a significant increase in granuloma sizes. An analysis of cytokine secretions in the lung showed that levels of IL-1β, IL-5, IL-6, and IL-10 had also increased [72]. These results suggested that Sj16 downregulates the inflammatory immune response against schistosome eggs, which corroborates earlier results [71].…”

Transmission-Blocking Vaccines against Schistosomiasis Japonica

“…Similarly, RNA sequencing analysis has been utilised to understand the immune cell response to infection, re-infection, and vaccine interaction through cellular transcriptome profiling. CRISPR-Cas, a gene-editing tool, provides a more effective, efficient, and accurate method of genome editing with potential application in Schistosoma research by adding to the available tool for discovering new vaccine targets and predicting host response to vaccines [201,[214][215][216]. The recently completed genomic sequences of schistosomes [217][218][219] provide a solid study base for the identification of more potential schistosome genes/proteins as vaccine targets.…”