Murine schistosomiasis mansoni: experimental analysis of bone marrow and peripheral myelopoiesis

Dutra, Hélio S.; El-Cheikh, Márcia Cury; Azevedo, Silvia P.; Rossi, Maria Isabel D.; Borojević, Radovan

doi:10.1007/s004360050467

Cited by 9 publications

(8 citation statements)

References 16 publications

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“…Many studies have demonstrated that MDSC play key roles in the inhibition of anti-tumor immunity [22]–[24] through a variety of mechanisms including nutrient starvation [25], the generation of reactive oxygen and nitrogen species (ROS and RNOS) [26], [27], and the induction of regulatory T cells [28], [29]. There are few reports of MDSC in parasitic infections, such as Schistosoma [30]–[32], Leishmania donaovani [33], [34], and Toxoplasma gondii [35]–[37]. However, the MDSC-like cells in Schistosoma mansoni or Leishmania donaovani infections have not been well defined.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2013

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“…To evaluate the kinetics of granuloma formation, we performed morphometry in lesions at three different time points (6, 8 and 12 weeks after infection), corresponding to the early and late acute phases, and to the early chronic phase of this process, respectively (Dutra et al, 1998). The dynamics of granuloma formation depends on the assembly of various types of cells, their in situ proliferation, and on the generation of connective tissue matrix.…”

Section: Discussionmentioning

confidence: 99%

Hepatic granulomas induced by Schistosoma mansoni in mice deficient for connexin 43 present lower cell proliferation and higher collagen content

Oloris¹,

Mesnil²,

Reis³

et al. 2007

Life Sciences

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“…Indeed, the helminth Schistosoma mansoni was shown to increase the number of bone marrow GM-CFU during the acute infection phase -correlating with increased M-CSF (or CSF-1) and IL-3 levels -which then return to normal levels during the chronic phase [26,27]. Interestingly, the extramedullary myelopoiesis in spleen and liver gradually increases throughout the course of infection [28]. An intriguing observation is the presence of high levels of GM-CFU in the liver granulomas (higher than in femurs) during the chronic infection phase, which are locally supported by GM-CSF and cell membrane-associated proteoglycans [26,29,30].…”

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confidence: 99%

Myeloid‐derived suppressor cells in parasitic infections

et al. 2010

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BelgiumMyeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that share a common property of suppressing immune responses. Several helminth and protozoan parasite species have developed efficient strategies to increase the rate of medullary or extramedullary myelopoiesis and to induce the expansion and accumulation of immature myeloid cells such as MDSC. In this review, we examine current knowledge on the factors mediating enhanced myelopoiesis and MDSC induction and recruitment during parasitic infections and how the MDSC phenotype and mechanism of immune modulation and suppression depends on the factors they encounter within the host. Finally, we place MDSC expansion in the context of the critical balance between parasite elimination and pathogenicity to the host and suggest attractive avenues for future research.Key words: Myeloid-derived suppressor cells . Myelopoiesis . Parasitic infection .T-cell suppression IntroductionParasitic infections are notoriously associated with suppression of immune responses. Populations of mature myeloid cells, such as macrophages in various activation states, are capable of displaying immunosuppressive features, and as a result play important roles in the critical balance between parasite elimination and pathogenicity to host tissues [1][2][3]. Heterogeneous populations of immature myeloid cells, characterized by the surface expression of both Gr-1 and CD11b molecules in mice and a shared potent immune-suppressing activity in vitro and in vivo, have been recognized to arise as a conserved response to various insults, including cancer, bacterial and parasitic infections. Collectively, these cells have been termed myeloid-derived suppressor cells (MDSC) [4]. A number of factors complicate the analysis of MDSC biology. First, MDSC are a heterogeneous mixture of immature myeloid cells that are in various intermediate stages of myeloid cell differentiation (reflected by expression of various levels of macrophage and DC markers such as F4/80 and CD11c, respectively, as well as MHC class II, CD80/86) and murine MDSC consist of different subpopulations with varying levels of reactivity with the Gr-1 monoclonal antibody. This Gr-1 antibody binds a common epitope on the Ly6G and Ly6C antigens [5]. Using antibodies specifically recognizing Ly6C or Ly6G, MDSC have been shown to contain at least two main subfractions: the CD11b suppressive capacity in all tumor models [7,16]. The heterogeneity and plasticity of MDSC and the lack of markers to optimally distinguish MDSC from other, more mature myeloid cell types, render T-cell anti-proliferative activity to be the ultimate defining characteristic of MDSC. Despite the above-mentioned limitations, the impact of MDSC on immune responses has made MDSC the topic of intense research. To date, most of the attention has been focused on cancer-associated MDSC, whereas relatively few studies have reported the activation, phenotype and especially the role of MDSC during parasitic infections (Table 1). In thi...

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Murine schistosomiasis mansoni: experimental analysis of bone marrow and peripheral myelopoiesis

Cited by 9 publications

References 16 publications

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

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

Hepatic granulomas induced by Schistosoma mansoni in mice deficient for connexin 43 present lower cell proliferation and higher collagen content

Myeloid‐derived suppressor cells in parasitic infections

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