Arginase promotes immune evasion of Echinococcus granulosus in mice

Abstract

Background: Cystic echinococcosis is a chronic disease caused by infection with the larvae of Echinococcus granulosus. The parasite's ability to establish persistent infection is partly due to its evolving immune evasion strategies. One strategy may involve the protective effect of arginase, which impedes the control of pathogens or tumors, whereas it remains largely unknown during E. granulosus infection. Here, we analyzed whether arginase was produced in peritoneal cells and assessed its role in immunosuppression in mice infected with protoscoleces of E. granulosus. Methods: BALB/c mice injected with protoscoleces of E. granulosus were used to evaluate the expression of arginase (ARG) in mRNA and protein levels. The profiles of ARG-1 expression in peritoneal cells and CD3ζ expression in T cells from spleens were assessed at different time points (3, 6, 9 and 12 months post-infection) by flow cytometry. In vitro, peritoneal cells were co-cultured with purified T cells in a transwell system, and the levels of CD3ζ re-expression were compared by flow cytometry. Meanwhile, the changes of l-arginine and its related metabolites in serum were tested. Results: Compared to the control group, the peritoneal cells from infected mice showed higher levels of ARG-1 mRNA and protein, unchanged ARG-2 and iNOS. Enhanced ARG-1 expression was present in SSC low

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

“…In view of the emerging immunometabolism perspective, the function of immune cells is governed by metabolic pathways ( 19 ), which are specifically regulated by rate-limiting enzymes. For example, arginase was recently shown to promote the immune evasion of E. granulosus in mice by inhibiting the expression of the T cell receptor CD3ζ chain ( 47 ). Our recent studies showed that the reprogramming of glucose and lipid metabolism has been linked to liver fibrosis in mice infected with S. japonicum ( 48 , 49 ).…”

Transcriptome analysis of Echinococcus granulosus sensu stricto protoscoleces reveals differences in immune modulation gene expression between cysts found in cattle and sheep

“…No differences in the expression of arginase-2 was found. However, arginase-1 isoform was differentially expressed, promoting immune modulation of E. granulosus in mice by inhibiting the expression of T cell receptor CD3ζ chain and antagonism against iNOS [ 35 ]. The expression of arginase was not measured in PSC and to the best of our knowledge, no previous work investigated the expression of arginase-2 in PSC.…”

Echinococcus granulosus Protoscoleces-Derived Exosome-like Vesicles and Egr-miR-277a-3p Promote Dendritic Cell Maturation and Differentiation

“…The percentage of DCs was found to increase in the liver leukocytes of mice infected with E. granulosus . Moreover, a previous related study demonstrated that these DCs highly express ARG-1, which inhibited the T cell response to E. granulosus antigens [ 4 ]. Therefore, E. granulosus PSC-ELVs induce the production of stimulatory DCs, which might serve as a new strategy to enhance the anti-parasitic immunity.…”

“…E. granulosus has evolved complex strategies to escape host immune responses, primarily by directing and manipulating the immune response towards tolerance or anergy. Recent research has demonstrated numerous immunoregulatory mechanisms related to macrophages, dendritic cells (DCs), and regulatory T cells (Tregs) [ 2 , 3 , 4 ]. The early immune response of E. granulosus infection shows Th1-oriented Th2-type responses [ 5 ].…”

“…E. granulosus oncospheres and cysts could modulate DCs maturation and alter monocyte differentiation to escape the host’s immunosurveillance and promote chronic infection [ 6 ]. Prior research by the study investigators showed that the numbers of macrophages, DCs, Tregs, and myeloid-derived suppressor cells (MDSCs) increased in BALB/c mice infected by E. granulosus [ 2 , 4 ], and the expression of arginase-1 (ARG-1) in many kinds of myeloid cells was enhanced, which inhibited the T cell response to E. granulosus antigens [ 4 ]. It was also previously found that the E. granulosus excretory–secretory (ES) products could induce immune tolerance in DCs to impair the host’s immune response [ 7 ]; however, whether some components of the ES products such as microRNAs (miRNAs) could promote the differentiation and maturation of DCs remains unclear.…”