Surveillance on the status of immune cells after Echinnococcus granulosus protoscoleces infection in Balb/c mice

• Published in: PloS one 2013-03, Vol.8 (3), p.e59746-e59746
• Main Authors: Pan, Wei, Zhou, He-Jun, Shen, Yu-Juan, Wang, Ying, Xu, Yu-Xin, Hu, Yuan, Jiang, Yan-Yan, Yuan, Zhong-Ying, Ugwu, Chidiebere E, Cao, Jian-Ping
• Format: Article
• Language: English
• Subjects: Adaptive Immunity; Animals; Antigen-presenting cells; Antigen-Presenting Cells - parasitology; Antigens; Biology; Bone marrow; Cancer; CD11b antigen; CD11b Antigen - metabolism; CD11c antigen; CD11c Antigen - metabolism; CD25 antigen; CD4 antigen; CD40L protein; CD44 antigen; CD69 antigen; CD8 antigen; Cell Proliferation; Complications; Cysts; Cytokines; Cytometry; Disease control; Disease prevention; Echinococcosis; Echinococcosis - immunology; Echinococcus granulosus; Excretory products; Female; Flow Cytometry; Foxp3 protein; Gene Expression Regulation; Histocompatibility Antigens Class II - immunology; Immune response; Immune status; Immune system; Immunity; Immunity, Innate; Immunoregulation; Immunosuppression; Immunosuppressive Agents - therapeutic use; Infections; L-selectin; Laboratory animals; Larvae; Leishmania donovani; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Malaria; Medicine; Mice; Mice, Inbred BALB C; Parasites; Parasitic diseases; Pathogenicity; Pathogens; Spleen - cytology; Suppressor cells; T-Lymphocytes - cytology; Time Factors; Tropical diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0059746

Cystic 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. In 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. Our 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.