Immunodepression, high IgM levels and evasion of the immune response in murine trypanosomiasis

Hudson, K.M.; Byner, Carole; Freeman, Joan; Terry, R. J.

doi:10.1038/264256a0

Cited by 158 publications

(83 citation statements)

References 15 publications

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“…Despite the hostile environment of the host's bloodstream, these extracellular parasites evade the immune response and establish a chronic infection through a combination of Ag variation of their variant-specific glycoprotein surface coat and induction of a generalized state of immunosuppression (11). Trypanosoma congolense-induced immunosuppression has been described in natural cattle infections as well as in experimental rodent infections (12)(13)(14). This suppression affects both cytokine production and T cell proliferation.…”

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confidence: 99%

African Trypanosomiasis: Naturally Occurring Regulatory T Cells Favor Trypanotolerance by Limiting Pathology Associated with Sustained Type 1 Inflammation

Guilliams

Oldenhove²,

Noël

et al. 2007

The Journal of Immunology

120

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Tolerance to African trypanosomes requires the production of IFN-γ in the early stage of infection that triggers the development of classically activated macrophages controlling parasite growth. However, once the first peak of parasitemia has been controlled, down-regulation of the type 1 immune response has been described. In this study, we have evaluated whether regulatory T cells (Tregs) contribute to the limitation of the immune response occurring during Trypanosoma congolense infection and hereby influence the outcome of the disease in trypanotolerant C57BL/6 host. Our data show that Foxp3+ Tregs originating from the naturally occurring Treg pool expanded in the spleen and the liver of infected mice. These cells produced IL-10 and limited the production of IFN-γ by CD4+ and CD8+ effector T cells. Tregs also down-regulated classical activation of macrophages resulting in reduced TNF-α production. The Treg-mediated suppression of the type 1 inflammatory immune response did not hamper parasite clearance, but was beneficial for the host survival by limiting the tissue damages, including liver injury. Collectively, these data suggest a cardinal role for naturally occurring Tregs in the development of a trypanotolerant phenotype during African trypanosomiasis.

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confidence: 99%

African Trypanosomiasis: Naturally Occurring Regulatory T Cells Favor Trypanotolerance by Limiting Pathology Associated with Sustained Type 1 Inflammation

Guilliams

Oldenhove²,

Noël

et al. 2007

The Journal of Immunology

120

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“…VSG molecules are expressed as an array of homodimers, tethered by GPI anchors to the extracellular surface of the trypanosome plasma membrane, forming a dense glycoprotein coat that protects the membrane of the parasite from the host environment (6,7). Early during infection, a strong and effective host immune response is mounted against the parasite that includes B cell and Th1 cell stimulation by VSG determinants in addition to macrophage activation, resulting in destruction of trypanosomes expressing the target VSG (8,9). However, trypanosomes undergo antigenic variation in which they express new VSG genes from a library of up to 10 3 different surface Ag genes, effectively ensuring that the host immune response does not fully eliminate the organisms.…”

mentioning

confidence: 99%

Glycosylinositolphosphate Soluble Variant Surface Glycoprotein Inhibits IFN-γ-Induced Nitric Oxide Production Via Reduction in STAT1 Phosphorylation in African Trypanosomiasis

Coller

Mansfield

Paulnock

2003

The Journal of Immunology

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Macrophages are centrally involved in the host immune response to infection with Trypanosoma brucei rhodesiense, a protozoan parasite responsible for human sleeping sickness in Africa. During trypanosome infections, the host is exposed to parasite-derived molecules that mediate macrophage activation, specifically GPI anchor substituents associated with the shed variant surface glycoprotein (VSG), plus the host-activating agent IFN-γ, which is derived from activated T cells and is essential for resistance to trypanosomes. In this study, we demonstrate that the level and timing of exposure of macrophages to IFN-γ vs GPI ultimately determine the macrophage response at the level of induced gene expression. Treatment of macrophages with IFN-γ followed by GIP-sVSG (the soluble form of VSG containing the glycosylinositolphosphate substituent that is released by parasites) stimulated the induction of gene expression, including transcription of TNF-α, IL-6, GM-CSF, and IL-12p40. In contrast, treatment of macrophages with GIP-sVSG before IFN-γ stimulation resulted in a marked reduction of IFN-γ-induced responses, including transcription of inducible NO synthase and secretion of NO. Additional experiments revealed that the inhibitory activity of GIP-sVSG was associated with reduction in the level of STAT1 phosphorylation, an event required for IFN-γ-induced macrophage activation. These results suggest that modulation of specific aspects of the IFN-γ response may be one mechanism by which trypanosomes overcome host resistance during African trypanosomiasis.

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“…Other investigators have reached a similar conclusion with respect to the effects of T. brucei (18,34). Characterization of these substances and further elucidation of their actions on immunocompetent cells is important both from the standpoint of understanding and controlling parasitic diseases and from the standpoint that such substances could be helpful in understanding and managing various diseases having an immunological basis.…”

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confidence: 68%

Mechanisms of trypanosome-mediated suppression of humoral immunity in mice

Albright

Dusanic

1978

Proc. Natl. Acad. Sci. U.S.A.

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Immunodepression, high IgM levels and evasion of the immune response in murine trypanosomiasis

Cited by 158 publications

References 15 publications

African Trypanosomiasis: Naturally Occurring Regulatory T Cells Favor Trypanotolerance by Limiting Pathology Associated with Sustained Type 1 Inflammation

African Trypanosomiasis: Naturally Occurring Regulatory T Cells Favor Trypanotolerance by Limiting Pathology Associated with Sustained Type 1 Inflammation

Glycosylinositolphosphate Soluble Variant Surface Glycoprotein Inhibits IFN-γ-Induced Nitric Oxide Production Via Reduction in STAT1 Phosphorylation in African Trypanosomiasis

Mechanisms of trypanosome-mediated suppression of humoral immunity in mice

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