The Toxoplasma gondii Peptide AS15 Elicits CD4 T Cells That Can Control Parasite Burden

Grover, Harshita Satija; Blanchard, Nicolas; González, Federico; Chan, Shiao Wei; Robey, Ellen; Shastri, Nilabh

doi:10.1128/iai.00425-12

Cited by 59 publications

(68 citation statements)

References 63 publications

(61 reference statements)

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“…We used MHCI tetramers that bind CD8 + T lymphocytes specific for the endogenous T. gondii epitope Tgd057 and MHCII tetramers that bind CD4 + T cells specific for the Toxoplasma epitope CD4Ag28m (35, 36). The frequency of parasite-specific CD4 + and CD8 + T cells was equivalent in Ex3 DC−/− and Ex3 fl/fl mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

β-Catenin Signaling Drives Differentiation and Proinflammatory Function of IRF8-Dependent Dendritic Cells

Cohen

Smith

McDougal

et al. 2015

The Journal of Immunology

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β-catenin signaling has recently been tied to the emergence of tolerogenic dendritic cells (DC). Here we demonstrate a novel role for β-catenin in directing DC subset development through IRF8 activation. We found that splenic DC precursors express β-catenin, and DC from mice with CD11c-specific constitutive β-catenin activation upregulated IRF8 through targeting of the Irf8 promoter, leading to in vivo expansion of IRF8-dependent CD8α+, plasmacytoid, and CD103+CD11b− DC. β-catenin-stabilized CD8α+ DC secreted elevated IL-12 upon in vitro microbial stimulation, and pharmacological β-catenin inhibition blocked this response in WT cells. Upon infections with Toxoplasma gondii and vaccinia virus, mice with stabilized DC β-catenin displayed abnormally high Th1 and CD8+ T lymphocyte responses, respectively. Collectively, these results reveal a novel and unexpected function for β-catenin in programming DC differentiation towards subsets that orchestrate proinflammatory immunity to infection.

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Section: Resultsmentioning

confidence: 99%

β-Catenin Signaling Drives Differentiation and Proinflammatory Function of IRF8-Dependent Dendritic Cells

Cohen

Smith

McDougal

et al. 2015

The Journal of Immunology

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“…Moreover, Grover et al (2012) reported decreased parasite load in vaccinated mice due to increased level of CD4? T-lymphocytes in response to vaccination by single parasite peptide (AS15), which is one of the constituent of ESA.…”

Section: Discussionmentioning

confidence: 99%

A comparative study between excretory/secretory and autoclaved vaccines against RH strain of Toxoplasma gondii in murine models

et al. 2013

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Toxoplasma gondii is an obligate intracellular protozoan that has a major importance in public health, in addition to veterinary medicine. Therefore, the development of an effective vaccine for controlling toxoplasmosis is an important goal. Excretory/secretory antigens (ESA), were previously identified as potential vaccine candidates, proved to play important roles in the pathogenesis and immune escape of the parasite. In addition, autoclaved Toxoplasma vaccine (ATV) is a special type of killed vaccine, recently characterized. The aim of the present work was, to compare between excretory/secretory and ATV against RH strain of T. gondii in mice based on; parasitological and histopathological levels. Tachyzoites were harvested from peritoneal exudates of infected mice and were used for challenge infection and vaccine preparation. BCG was used as an adjuvant. Mice were allocated equally into five groups; they were vaccinated intradermally over the sternum. The results of this study showed that the survival time after challenge, extended up to 16 days in ESA vaccinated group and up to 15 days in autoclaved Toxoplasma vaccinated group. ESA vaccinated group exhibited a profound decrease in parasite load following parasite challenge with a higher percentage of reduction in parasite count in all examined organs than the autoclaved Toxoplasma vaccinated group. The histopathological picture of the liver in both immunized groups, revealed marked reduction in the pathological changes observed as compared to controls, especially in ESA vaccinated group. It was concluded that vaccination with ESA showed more promising results versus ATV, as demonstrated by the survival rate of vaccinated mice, tachyzoites count and histopathological examination.

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“…In contrast to H-2 d mice, in which the CD8 T cell response dominates over the CD4 T cell response (Blanchard et al, 2008), B6 mice generated a robust CD4 T cell response but a weaker CD8 response towards T. gondii (Figure 1A, top panels; (Grover et al, 2012). To selectively expand the CD8 T cells, we used MHC Class II deficient dendritic cells as APCs for in vitro restimulations.…”

Section: Resultsmentioning

confidence: 97%

“…with 1-5×10 6 irradiated tachyzoites of the Type II Prugniuad-tomato-OVA strain (Pru) as described (Grover et al, 2012). For inducing protection, mice were immunized in the footpad with activated B6 bone-marrow derived dendritic cells (BMDCs) loaded with synthetic peptide as described (Blanchard et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

Impact of Regulated Secretion on Antiparasitic CD8 T Cell Responses

et al. 2014

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Summary CD8 T cells play a key role in defense against the intracellular parasite Toxoplasma but why certain CD8 responses are more potent than others is not well understood. Here, we describe a parasite antigen ROP5 that elicits a modest CD8 T cell response in genetically susceptible mice. ROP5 is secreted via parasite organelles termed rhoptries that are injected directly into host cells during invasion, whereas the protective, dense granule antigen, GRA6, is constitutively secreted into the parasitophorous vacuole. Transgenic parasites in which the ROP5 antigenic epitope was targeted for secretion through dense granules led to enhanced CD8 T cell responses, whereas targeting the GRA6 epitope to rhoptries led to reduced CD8 responses. CD8 T cell responses to the dense granule-targeted ROP5 epitope resulted in reduced parasite load in the brain. These data suggest that the mode of secretion impacts the efficacy of parasite-specific CD8 T cell responses.

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The Toxoplasma gondii Peptide AS15 Elicits CD4 T Cells That Can Control Parasite Burden

Cited by 59 publications

References 63 publications

β-Catenin Signaling Drives Differentiation and Proinflammatory Function of IRF8-Dependent Dendritic Cells

β-Catenin Signaling Drives Differentiation and Proinflammatory Function of IRF8-Dependent Dendritic Cells

A comparative study between excretory/secretory and autoclaved vaccines against RH strain of Toxoplasma gondii in murine models

Impact of Regulated Secretion on Antiparasitic CD8 T Cell Responses

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