Surveillance on the Status of Immune Cells after Echinnococcus granulosus Protoscoleces Infection in Balb/c Mice

Abstract

BackgroundCystic echinococcosis is a global parasitic disease caused by infection with Echinococcus granulosus larvae with potentially life-threatening complications in humans. To date, the status of the immune cells believed to be associated with the pathogenicity of E. granulosus infection has not been demonstrated clearly.Methodology/Principal FindingsIn this study, we developed a multiplex flow cytometry assay to investigate the systemic immune status of innate and adaptive immunity at 30, 180, 360 days post-infection (dpi) in mice infected with E. granulousus. At 30 dpi, an increase in the number of CD11b+ and CD11c+ antigen-presenting cells (APCs) was observed. This was accompanied by the slight down-regulated expression of the co-stimulatory molecule MHC-II, indicating the impairment of APCs in early infection through the release of secretory-excretory products. In all infected groups, we observed a significant increase in innate immune cells, including APCs and GR-1+ cells, and a dramatic increase in the myeloid-derived suppressor cells (MDSC) expressing CD11b+/GR-1+. Moreover, the upregulation of the activated markers CD69, CD44, CD40L, and the downregulation of CD62L were observed in the CD4+ and CD8+ T cells following infection. Regulatory T cells expressing CD4+/CD25+/FoxP3 + increased significantly over the course of infection.ConclusionsOur findings demonstrate that the microenvironment in the peripheral immune system after E. granulosus infection changes in subtle but detectably ways, especially during the persistent period of infection. We found that T cells were activated following infection, but observed that the significant increase of immunosuppressive cells such as MDSC and Treg cells could inhibit T cell response to E. granulosus antigens. We suggest these cells may play a neglected but key role in the downregulation of the immune response in long-term parasitic infection. Understanding the basic functions and temporal interactions of these immunosuppressive cells will pave the way for new strategies of parasite vaccine design.

Co‐existence of Echinococcus granulosus infection and cancer metastasis in the liver correlates with reduced Th1 immune responses

“…These cells can accumulate in the spleen and in the liver (23). Tregs and MDSCs are also detected in early peritoneal immune responses against experimental E. granulosus infection (6,28). While we did not check the status of MDSCs, high levels of CD4 + lymphocytes, especially the CD25 + CD4 + T cells, were observed in the liver of the mice from the Echinococcus infection and breast cancer group.…”

Echinococcosis

“…Moreover, PSC present Fc-binding activity (Baz et al 1998) and express immune regulatory antigen B and EgTeg (Ortona et al 2005;Sanchez et al 1991;Monteiro et al 2010). Recently, T-regulatory and myeloid-derived suppressor cells have been found to be systemically expanded in mice with E. granulosus infection and in CE patients (Pan et al 2013;Tuxun et al 2012). Taken together, these results support the presence of an immunomodulatory environment downregulating both Th1 and Th2 responses and favoring parasite survival.…”

Pro-Angiogenic Activity of Monocytic-Type Myeloid-Derived Suppressor Cells from Balb/C Mice Infected with Echinococcus Granulosus and the Regulatory Role of miRNAs

“…Single cell suspensions were prepared from the murine spleens after 8 months of infection with E. granulosus protoscoleces and from normal murine spleens (control group), as published previously [5]. Then, M-MDSCs were collected according to the instructions of the mouse Myeloid-Derived Suppressor Cell Isolation Kit (Miltenyi Biotec, Germany), and the cells were incubated with the following anti-mouse antibodies: PE-Gr-1, FITC-CD11b, APC-Ly-6G and PerCP-Cy5.5-Ly-6C.…”

“…The molecular mechanisms underlying its development and pathogenesis are still unclear [1][2][3], although it has been reported that this parasite can successfully escape host immune responses, and a number of immunoregulatory mechanisms related to macrophages and dendritic cells as well as regulatory T cells are potentially involved [2]. In our previous studies, we found that hydatid cysts of E. granulosus could promote the formation of tubes from human umbilical vein endothelial cells (HUVECs) in vitro [4], and that myeloid-derived suppressor cells (MDSCs) were significantly enriched in the spleen and peripheral blood of Balb/c mice infected with E. granulosus and played an immunosuppressive role [5]. The in vitro results are supported by other studies which have shown that angiogenesis is critical for parasites to acquire the nutrients necessary for growth, maturity and breeding after infection [6].…”