Metabolomics Analysis of Splenic CD19+ B Cells in Mice Chronically Infected With Echinococcus granulosus sensu lato Protoscoleces

Abstract

Background: The larval stages of Echinococcus granulosus sensu lato (E. granulosus s.l) infection can alter B cell function and affect host anti-infective immunity, but the underlying mechanism remains unclear. The newly emerging immunometabolism highlights that several metabolites are key factors in determining the fate of immune cells, which provides a new insight for exploring how larval E. granulosus s.l. infection remodels B cell function. This study investigated the metabolomic profiles of B cells in mice infected with E. granulosus s.l. protoscoleces (PSC).Results:Total CD19+ B cells, purified from the spleen of infected mice, showed significantly increased production of IL-6, TNF-α, and IL-10 after exposure to LPS in vitro. Moreover, the mRNA expression of metabolism related enzymes in B cells was remarkably disordered post infection. In addition, differential metabolites were identified in B cells after infection. There were 340 differential metabolites (83 upregulated and 257 downregulated metabolites) identified in the positive ion model, and 216 differential metabolites (97 upregulated and 119 downregulated metabolites) identified in the negative ion mode. Among these, 64 differential metabolites were annotated and involved in 68 metabolic pathways, including thyroid hormone synthesis, the metabolic processes of glutathione, fructose, mannose, and glycerophospholipid. Furthermore, several differential metabolites such as glutathione, taurine, and inosine were validated to regulate the cytokine production in LPS stimulated B cells.Conclusion:Infection with the larval E. granulosus s.l. causes metabolic reprogramming in the intrinsic B cells of mice, which provides the first evidence for understanding the role and mechanism of B cells in parasite anti-infective immunity from the viewpoint of immunometabolism.

Transcriptomic Profiles of Splenic CD19+ B Cells in Mice Chronically Infected With the Larval Echinococcus granulosus

“…Furthermore, most DEGs related to inflammation and chemotaxis were significantly upregulated after infection. These results were consistent with our previous results that LPS stimulates infected B cells to produce both high levels of pro-inflammatory and anti-inflammatory cytokines ( 25 ).…”

“…Furthermore, intimate interaction between these genes of immune and metabolism was shown by co-expression network analysis. Correspondingly, our recent study also identified lots of differential metabolites associated with the functional differentiation and lipid metabolism in the splenic B cells post the parasitic infection ( 25 ). Overall, these findings primarily established the potential functional link of metabolic events and B cells' differentiation and function in response to the long-term infection of the larval E. granulosus .…”

“…Agpat4/LPA axis in colorectal cancer cells has been validated to regulate p38/p65 signaling-dependent macrophage polarization ( 30 ). Besides, in our previous study, 13 differential metabolites involved in lipid metabolism were identified in splenic B cells upon larval E. granulosus infection ( 25 ). These results indicated that larval E. granulosus infection can reprogram lipid metabolism in B cells, thereby modulating its immune function.…”

“…B cells represent important regulatory cells that mediate the anti-parasite immune response ( 24 ). Our previous studies have shown that larval E. granulosus infection induces function changes of B cell function, and notably, numerous differential metabolites were identified in splenic B cells of infected mice ( 25 ). To further investigate the specific downstream mechanism of E. granulosus on B cell function, total CD19 + B cells in spleens were collected from Eg infected and control mice for the RNA sequencing analysis.…”

“…Our previous study found an accumulation of IL-10 + CD19 + B cells post larval E. granulosus infection ( 3 ). Both the inflammatory cytokines (TNF-α, IL-6) and anti-inflammatory cytokines (IL-10) production were significantly elevated in B cells of infected mice after exposure to LPS ( 25 ). These results implicated that the parasitic infection alters B cell function.…”