Induction of protective immunity by DNA vaccination with Toxoplasma gondii HSP70, HSP30 and SAG1 genes

Mohamed, Rabie M.; Aosai, Fumie; Chen, Mei; Mun, Hye-Seong; Norose, Kazumi; Belal, Usama S.; Li, Piao; Yano, Akihiko

doi:10.1016/s0264-410x(03)00157-9

Cited by 83 publications

(42 citation statements)

References 50 publications

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“…We have developed a DNA vaccine encoding a virulent HSP70 molecule specific for tachyzoites (i.e., the pathogenic stage of T. gondii at the acute phase or at acute exacerbation of the chronic phase of infection) targeting epidermal and dermal DC against T. gondii infection (25,31,32). The T. gondii HSP70 gene vaccine is proven to induce in vivo DC activation and successive Th1 cell polarization in the dLN, and the vaccine effects persist to the chronic phase of toxoplasmosis (31).…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii Infection Inhibits Th17-Mediated Spontaneous Development of Arthritis in Interleukin-1 Receptor Antagonist-Deficient Mice

et al. 2012

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ABSTRACTInterleukin 1 receptor antagonist (IL-1Ra)-deficient BALB/c mice develop spontaneous arthritis resembling human rheumatoid arthritis. We herein report that infection withToxoplasma gondii, an intracellular protozoan, is capable of ameliorating the spontaneous development of arthritis in IL-1Ra-deficient mice. The onset of arthritis development was delayed and the severity score of arthritis was significantly suppressed inT. gondii-infected mice. Expression of IL-12p40 mRNA from CD11c+cells of mesenteric lymph nodes (mLN) and spleen markedly increased at 1 week after peroral infection. While CD11c+cells also produced IL-10, IL-1β, and IL-6, CD4+T cells fromT. gondii-infected mice expressed significantly high levels of T-bet and gamma interferon (IFN-γ) mRNA in both mLN and spleen. Levels of GATA-3/IL-4 mRNA or RORγt/IL-17 mRNA decreased in the infected mice, indicating Th1 cell polarization and the reduction of Th2 and Th17 cell polarization. The severity of arthritis was related to Th1 cell polarization accompanied by Th17 cell reduction, demonstrating the protective role of theT. gondii-derived Th1 response against Th17 cell-mediated arthritis in IL-1Ra-deficient mice.

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Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii Infection Inhibits Th17-Mediated Spontaneous Development of Arthritis in Interleukin-1 Receptor Antagonist-Deficient Mice

et al. 2012

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“…By using a gene gun, we successfully developed a vaccine with T.g.HSP70 gene against T. gondii infection, targeting epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) (Mohamed et al 2003). The induction of protective immunity by T.g.HSP70 gene suggested the presence of receptor expression for T.g.HSP70 on peripheral immature DCs (LC/DC).…”

Section: Introductionmentioning

confidence: 99%

Toxoplasma gondii–derived heat shock protein 70 stimulates maturation of murine bone marrow–derived dendritic cells via Toll-like receptor 4

et al. 2006

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Toxoplasma gondii -derived heat shock protein 70 (T.g.HSP70) induced maturation of bone marrow-derived dendritic cells (DCs) of wild-type (WT) C57BL/6 mice as evidenced by an increase in surface expression of MHC class I and II molecules and costimulatory molecules such as CD40, CD80, and CD86. Functionally, decreased phagocytic ability and increased alloreactive T cell stimulatory ability were observed in T.g.HSP70-stimulated DCs. These phenotypic and functional changes of T.g.HSP70-stimulated DCs were demonstrated in Toll-like receptor (TLR) 2-and myeloid differentiation factor 88 (MyD88)-deficient but not TLR4-deficient C57BL/6 mice. DCs from WT and TLR2-deficient but not TLR4-deficient mice produced IL-12 after T.g.HSP70 stimulation. T.g.HSP70-stimulated DCs from WT, TLR2-deficient, and MyD88-deficient, but not TLR4-deficient mice expressed IFN-␤ mRNA. Thus, T.g.HSP70 stimulates murine DC maturation via TLR4 through the MyD88-independent signal transduction cascade.

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“…The only known related protein in protozoal parasites is Toxoplasma gondii Hsp30/bag1, which is selectively expressed by the bradyzoite stage (5). In mice, immunization with Hsp30/bag1 enhanced protective immunity against challenge (38,42).…”

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confidence: 99%

Conservation ofBabesia bovisSmall Heat Shock Protein (Hsp20) among Strains and Definition of T Helper Cell Epitopes Recognized by Cattle with Diverse Major Histocompatibility Complex Class II Haplotypes

et al. 2004

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Babesia bovis small heat shock protein (Hsp20) is recognized by CD4؉ T lymphocytes from cattle that have recovered from infection and are immune to challenge. This candidate vaccine antigen is related to a protective antigen of Toxoplasma gondii, Hsp30/bag1, and both are members of the ␣-crystallin family of proteins that can serve as molecular chaperones. In the present study, immunofluorescence microscopy determined that Hsp20 is expressed intracellularly in all merozoites. Importantly, Hsp20 is also expressed by tick larval stages, including sporozoites, so that natural tick-transmitted infection could boost a vaccine-induced response. The predicted amino acid sequence of Hsp20 from merozoites is completely conserved among different B. bovis strains. To define the location of CD4 ؉ T-cell epitopes for inclusion in a multiepitope peptide or minigene vaccine construct, truncated recombinant Hsp20 proteins and overlapping peptides were tested for their ability to stimulate T cells from immune cattle. Both amino-terminal (amino acids [aa] 1 to 105) and carboxyterminal (aa 48 to 177) regions were immunogenic for the majority of cattle in the study, stimulating strong proliferation and IFN-␥ production. T-cell lines from all individuals with distinct DRB3 haplotypes responded to aa 11 to 62 of Hsp20, which contained one or more immunodominant epitopes for each animal. One epitope, DEQTGLPIKS (aa 17 to 26), was identified by T-cell clones. The presence of strain-conserved T helper cell epitopes in aa 11 to 62 of the ubiquitously expressed Hsp20 that are presented by major histocompatibility complex class II molecules represented broadly in the Holstein breed supports the inclusion of this region in vaccine constructs to be tested in cattle.

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Induction of protective immunity by DNA vaccination with Toxoplasma gondii HSP70, HSP30 and SAG1 genes

Cited by 83 publications

References 50 publications

Toxoplasma gondii Infection Inhibits Th17-Mediated Spontaneous Development of Arthritis in Interleukin-1 Receptor Antagonist-Deficient Mice

Toxoplasma gondii Infection Inhibits Th17-Mediated Spontaneous Development of Arthritis in Interleukin-1 Receptor Antagonist-Deficient Mice

Toxoplasma gondii–derived heat shock protein 70 stimulates maturation of murine bone marrow–derived dendritic cells via Toll-like receptor 4

Conservation ofBabesia bovisSmall Heat Shock Protein (Hsp20) among Strains and Definition of T Helper Cell Epitopes Recognized by Cattle with Diverse Major Histocompatibility Complex Class II Haplotypes

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