Affinage · Toxoplasma gondii

HSP70

heat shock protein HSP70 · UniProt A0A125YXI9

Annotated
2026-09-08
60 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TgHSP70 is a stress-inducible ~72 kDa cytosolic molecular chaperone of Toxoplasma gondii that couples parasite stage conversion to modulation of host immunity and serves as a virulence factor (PMID:9632598, PMID:12097402). Its transcription is driven by a defined pH-responsive cis-regulatory element engaged by a putative DNA-binding protein, accounting for its induction during alkaline-pH-triggered bradyzoite development, while induction in vivo is independent of IFN-γ, TNF-α and reactive nitrogen intermediates (PMID:15003494, PMID:11428337, PMID:9632598). Within the parasite it operates as part of a cytosolic Hsp40(TgSis1)-Hsp70-Hsp90 chaperone complex, and its chaperone activity is required for intracellular multiplication, as shown by attenuation with the Hsp70-selective inhibitor PES that binds TgHSP70 directly (PMID:22209934, PMID:33157166). As a virulence factor, TgHSP70 directly binds host TLR4 (confirmed by LSPR and Co-IP) to activate TLR4/NF-κB signaling and, in virulent strains, suppresses host NF-κB-driven iNOS/NO-mediated killing while restraining tachyzoite-to-bradyzoite conversion (PMID:36933491, PMID:12097402). Acting on innate immune cells through TLR4, it functions as a MyD88-independent B cell mitogen and matures dendritic cells, and drives an IFN-γ-dependent, IgE-independent lethal anaphylaxis via a TLR4/MyD88/cPLA2/PAF cascade (PMID:12653480, PMID:16572725, PMID:16943259, PMID:18667035). The immunosuppressive/deleterious activity maps to the protein's carboxy-terminal region (PMID:10905074).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 Medium

    Establishing when TgHSP70 is expressed was the first step: its induction under alkaline pH stress and colocalization with bradyzoite antigens tied the chaperone to stage conversion.

    Evidence Western blot, IEM, RT-PCR and quercetin inhibition during in vitro and in vivo bradyzoite development

    PMID:9632598

    Open questions at the time
    • Whether HSP70 induction is a cause or consequence of differentiation was not resolved
    • Quercetin is not HSP70-specific
  2. 1998 Medium

    Genomic characterization defined the gene as single-copy with a strain-variable C-terminal repeat and higher transcription in virulent strains, hinting that HSP70 dosage tracks with virulence.

    Evidence Genomic library screening, sequencing, copy-number and mRNA analysis of RH vs ME49

    PMID:9724875

    Open questions at the time
    • Functional consequence of the repeat-length difference not tested
    • Post-transcriptional regulation inferred, not directly demonstrated
  3. 2000 Medium

    Immune-deficiency models showed HSP70 induction is not driven by host effector cytokines or nitrogen intermediates, indicating an intrinsic parasite stress response rather than an immune-triggered one.

    Evidence Western blot of tachyzoites from nude, SCID, IFN-γR KO and TNFR KO mice (RH strain)

    PMID:11428337

    Open questions at the time
    • The actual physiological inducer in vivo was not identified
  4. 2000 Low

    Domain mapping localized the deleterious effect on host protective immunity to the C-terminal region, first pointing to a discrete effector module.

    Evidence Immunization with recombinant N- vs C-terminal fragments, QC-PCR brain parasite load

    PMID:10905074

    Open questions at the time
    • Single quantification method with limited mechanistic follow-up
    • Molecular basis of C-terminal activity unknown
  5. 2000 Low

    Linking HSP70 to host NO suppression and mortality reframed it as a danger signal that blunts macrophage killing during lethal infection.

    Evidence NO release assay on peritoneal macrophages and mortality in IFN-γ KO mice

    PMID:11048655

    Open questions at the time
    • No receptor or signaling mechanism defined at this stage
    • Correlative mortality link
  6. 2002 Medium

    Antisense knockdown provided causal, strain-specific evidence that TgHSP70 suppresses host NF-κB/iNOS killing and restrains stage conversion in virulent but not avirulent strains.

    Evidence Antisense oligonucleotide knockdown in RH/ENT vs ME49/C with NF-κB, iNOS/NO and bradyzoite-conversion readouts

    PMID:12097402

    Open questions at the time
    • Molecular basis of virulent-vs-avirulent difference not fully explained
    • Antisense off-target effects not excluded
  7. 2004 Medium

    Identification of a pH-responsive cis-element and an interacting DNA-binding protein defined the transcriptional switch controlling stress induction of hsp70.

    Evidence Reporter deletion analysis, stable GFP reporter under pH-shock, and EMSA in RH strain

    PMID:15003494

    Open questions at the time
    • The DNA-binding protein was not molecularly identified
    • Element defined in RH only
  8. 2005 Medium

    Dissecting the receptor logic showed TgHSP70 drives macrophage NO via TLR2/MyD88/IRAK4 but induces tolerance via TLR4/SOCS-1, explaining how it both activates and later dampens macrophages.

    Evidence NO assays in TLR2/TLR4/MyD88/IRAK4 KO mice with SOCS-1 and JNK/IκBα phosphorylation readouts

    PMID:16040976

    Open questions at the time
    • Reconciliation of TLR2 vs TLR4 usage across cell types not fully resolved
  9. 2006 Medium

    Two studies established TLR4 as the mitogenic/maturation receptor, showing TgHSP70 acts as a MyD88-independent B cell mitogen and dendritic cell maturation stimulus.

    Evidence B cell/T cell proliferation and DC maturation assays in TLR4-mutant, TLR4-/-, TLR2-/- and MyD88-/- mice with polymyxin B controls

    PMID:12653480 PMID:16572725

    Open questions at the time
    • The MyD88-independent adaptor/signal downstream of TLR4 was not defined
    • LPS-contamination excluded only pharmacologically for some readouts
  10. 2008 Medium

    Anaphylaxis studies traced the lethal reaction to a TLR4/MyD88 (not TRIF) cascade activating cPLA2 via p38 and p44/42 MAPK to produce PAF, in an IFN-γ-dependent, IgE-independent manner.

    Evidence In vivo anaphylaxis in TLR4/TLR2/MyD88/TRIF/IFN-γ KO mice with cPLA2 phosphorylation, MAPK inhibitors, PAF receptor antagonist and adoptive transfer

    PMID:16943259 PMID:18667035

    Open questions at the time
    • The CD11b+ effector population's full role not delineated
    • Relevance to natural infection outcomes not established
  11. 2010 Medium

    Co-IP identified AIF and Apaf-1 as binding partners of infection-upregulated HSP70, defining a mechanism by which HSP70 inhibits mitochondrial apoptosis in host macrophages.

    Evidence Co-immunoprecipitation, subcellular fractionation and caspase-3/DNA fragmentation assays in THP-1 macrophages

    PMID:20680337

    Open questions at the time
    • Contribution of parasite vs host HSP70 to the anti-apoptotic effect not separated
    • No reciprocal Co-IP or mutagenesis
  12. 2011 Low

    Co-IP with TgSis1 placed TgHSP70 in a cytosolic Hsp40-Hsp70-Hsp90 chaperone complex, defining its physical role within the parasite proteostasis machinery.

    Evidence Co-immunoprecipitation, cytosolic fractionation and structural modeling of TgSis1

    PMID:22209934

    Open questions at the time
    • Single Co-IP without functional follow-up on HSP70
    • Client proteins of the complex not identified
  13. 2019 Medium

    An anti-parasitic role emerged: membrane Hsp70 on infected leukocytes triggers CD40-dependent, beclin1/ULK1-mediated autophagy in endothelial cells to restrict neural invasion, showing HSP70 can also drive host defense.

    Evidence In vivo infection with adoptive transfer, beclin1/ULK1 KO and anti-Hsp70 functional blocking

    PMID:31109947

    Open questions at the time
    • Whether the inducible Hsp70 is host- or parasite-derived not fully resolved
    • Reconciliation with immunosuppressive roles unclear
  14. 2020 Medium

    Chemical-genetic evidence with the Hsp70 inhibitor PES demonstrated that HSP70 chaperone function is required for intracellular parasite multiplication, engaging both host and parasite Hsp70.

    Evidence PES inhibition, biotinylated-PES binding to host and TgHSP70, host Hsp70 siRNA, molecular docking and autophagy assays

    PMID:33157166

    Open questions at the time
    • Parasite-autonomous requirement not isolated from host Hsp70 contribution
    • Client proteins driving multiplication unknown
  15. 2023 Medium

    Direct interaction studies established that TgHSP70 physically binds host TLR4 to activate TLR4/NF-κB signaling, providing the receptor-level mechanism for its pro-inflammatory virulence activity.

    Evidence Molecular docking, LSPR, Co-IP and coixol disruption with iNOS/TNF-α/HMGB1 readouts in RH strain

    PMID:36933491

    Open questions at the time
    • Binding interface not mapped to the C-terminal effector region
    • Shown in RH only
  16. 2024 Low

    bag1 knockout revealed that HSP70 is part of a compensatory stress-response network upregulated during bradyzoite differentiation, linking it to a redundant chaperone system in cyst formation.

    Evidence CRISPR/Cas9 bag1 KO in ME49 with qPCR of HSP family members during differentiation

    PMID:39080770

    Open questions at the time
    • HSP70 upregulation is a secondary observation; no direct HSP70 manipulation
    • Functional contribution to cyst formation not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the parasite's intrinsic chaperone function, its C-terminal TLR4-binding virulence activity, and its dual immunosuppressive vs autophagy-inducing effects are mechanistically integrated across strains and infection stages.
  • No structure of the TgHSP70-TLR4 interface
  • Chaperone client proteins in the parasite unidentified
  • Contribution of parasite vs host Hsp70 to each phenotype not cleanly separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
AIF (HOST) [#11]APAF-1 (HOST) [#11]HSP90 [#12]TGSIS1/HSP40 [#12]TLR4 (HOST) [#16]
Complex memberships
Cytosolic Hsp40(TgSis1)-Hsp70-Hsp90 chaperone complex [#12]

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 TgHSP70 (72 kDa protein) expression is induced during bradyzoite development in T. gondii under alkaline pH stress (pH 8.1), as demonstrated by Western blotting, immunofluorescence, immunoelectron microscopy, and RT-PCR; hsp70 colocalized with bradyzoite-specific antigens and was detected in bradyzoites isolated from mouse brain. Quercetin, which inhibits hsp70 synthesis, suppressed bradyzoite development in vitro. Western blot, immunofluorescence, immunoelectron microscopy, RT-PCR, pharmacological inhibition (quercetin) Infection and immunity Medium 9632598
1998 The cytoplasmic 70 kDa HSP gene is single-copy in both virulent (RH) and avirulent (ME49) strains; virulent strains have four copies of a 7-aa C-terminal repeat (GGMPGGM) vs. five in avirulent strains, and show 1.5–2-fold higher mRNA transcription in vivo and in vitro, indicating post-transcriptional regulation also occurs in T. gondii. Genomic DNA library screening, PCR amplification, gene sequencing, copy-number estimation, Northern/mRNA analysis International journal for parasitology Medium 9724875
1998 High-level TgHSP70 expression occurs during in vivo bradyzoite-to-tachyzoite conversion (reactivation) in chronically infected mice treated with neutralizing anti-IFN-γ or anti-TNF-α antibodies, demonstrating HSP70 upregulation is associated with stage conversion under immunosuppressive conditions. Immunocytochemistry, photometric assay of antigen expression in CNS tissue Infection and immunity Low 9673286
2002 Antisense oligonucleotide-mediated reduction of TgHSP70 expression in virulent T. gondii strains (RH, ENT) increased host NF-κB activation in splenocytes and iNOS/NO production in RAW 264.7 macrophages, and enhanced tachyzoite-to-bradyzoite conversion in vitro; these effects were not observed in avirulent strains (ME49, C), establishing TgHSP70 as a suppressor of host NF-κB and iNOS-mediated killing specifically in virulent strains. Antisense oligonucleotide transfection, Western blot (HSP70 expression), in vivo tachyzoite counting (spleen), in vitro bradyzoite conversion assay, iNOS mRNA measurement, NF-κB nuclear translocation assay, NO production assay Journal of immunology Medium 12097402
2000 TgHSP70 inhibits nitric oxide release from peritoneal macrophages of T. gondii-infected mice, and high-level TgHSP70 expression correlates with mortality in IFN-γ knockout mice, identifying TgHSP70 as a danger signal that suppresses host macrophage NO production during lethal acute infection. NO release assay (peritoneal macrophages), mRNA analysis (RT-PCR for stage markers), in vivo mortality analysis in IFN-γ KO mice Cell stress & chaperones Low 11048655
2002 TgHSP70 functions as a B cell mitogen, inducing proliferation of murine B cells (B220+) but not T cells via TLR4; this proliferation is MyD88-independent (unlike LPS-induced proliferation), polymyxin B-insensitive, and absent in TLR4-mutant (C3H/HeJ) and TLR4-/- mice. In vitro proliferation assay, cell subset depletion, TLR4-mutant and knockout mice, MyD88-/- mice, polymyxin B inhibition control Cell stress & chaperones Medium 12653480
2004 A pH-responsive cis-regulatory element was identified in the T. gondii hsp70 genomic locus upstream region by deletion analysis using β-galactosidase reporter constructs transiently transfected into RH strain T. gondii; GFP reporter constructs stably transfected into T. gondii showed pH-shock-induced GFP expression driven by this element. Gel-shift analysis identified a putative DNA-binding protein interacting with the pH-regulated region. Deletion analysis with β-galactosidase reporter, stable transfection with GFP reporter, electrophoretic mobility shift assay (EMSA/gel shift) International journal for parasitology Medium 15003494
2005 TgHSP70-induced macrophage NO production signals through TLR2, MyD88, and IRAK4 (not TLR4); however, TgHSP70-induced macrophage tolerance (suppression of NO on restimulation) is mediated through TLR4 and SOCS-1 upregulation, with JNK and IκBα phosphorylation occurring via TLR2 in the absence of TLR4-mediated tolerance. NO release assay, gene-knockout mice (TLR2-/-, TLR4-/-, MyD88-/-, IRAK4-/-), polymyxin B control, SOCS-1 expression assay, JNK and IκBα phosphorylation analysis Infection and immunity Medium 16040976
2006 TgHSP70 stimulates maturation of murine bone marrow-derived dendritic cells (increased MHC I/II, CD40, CD80, CD86 surface expression; decreased phagocytic ability; increased alloreactive T cell stimulation; IL-12 production; IFN-β mRNA expression) via TLR4 through a MyD88-independent signal transduction cascade; TLR2-/- and MyD88-/- DCs respond normally, but TLR4-/- DCs do not. DC maturation surface marker flow cytometry, phagocytosis assay, allostimulation assay, ELISA (IL-12), RT-PCR (IFN-β), TLR-deficient mouse DCs Cell stress & chaperones Medium 16572725
2006 TgHSP70 induces lethal anaphylactic reaction in T. gondii-infected mice through an IFN-γ-dependent, IgE-independent pathway involving platelet-activating factor (PAF); splenocytes (not serum) transfer this reactivity, and PAF receptor antagonist rescues mice from the reaction. In vivo anaphylaxis model, adoptive transfer (splenocytes vs. serum), IFN-γ KO mice, B cell-deficient mice, PAF receptor antagonist treatment, RT-PCR (PAF acetylhydrolase, IFN-γ mRNA) International immunology Medium 16943259
2008 TgHSP70-induced lethal anaphylactic reaction in infected mice is mediated via TLR4/MyD88-dependent (not TRIF-dependent) signaling, activating cPLA2 via p38 and p44/42 MAPK pathways in CD11b+ splenocytes, leading to PAF production; TLR4-/- and MyD88-/- mice are protected from the reaction. In vivo anaphylaxis model, TLR4-/-, TLR2-/-, MyD88-/-, TRIF-/- mice, cPLA2 phosphorylation assay, MAPK pathway inhibitors, PAF-AH mRNA expression Microbiology and immunology Medium 18667035
2010 In T. gondii-infected host cells (THP-1 macrophages), HSP70 (host-upregulated by infection) binds pro-apoptotic factors AIF and Apaf-1 (but not cytochrome c or procaspase-9) as shown by co-immunoprecipitation, inhibiting mitochondrial apoptosis by preventing AIF and cytochrome c release from mitochondria and suppressing caspase-3 activation in a parasite load-dependent manner. Western blot, DNA fragmentation assay, co-immunoprecipitation, caspase-3/7 activity assay, subcellular fractionation Parasitology research Medium 20680337
2011 TgSis1 (a T. gondii Hsp40/J-domain protein homologous to yeast Sis1) is a cytosolic chaperone that co-immunoprecipitates with T. gondii Hsp70 and Hsp90, establishing TgHSP70 as part of a cytosolic Hsp40-Hsp70-Hsp90 chaperone complex in the parasite. Co-immunoprecipitation, subcellular localization (cytosolic fractionation), structural modeling International journal of biological macromolecules Low 22209934
2020 TgHSP70 is required for intracellular multiplication of T. gondii: the Hsp70-selective inhibitor PES (2-phenylethynesulfonamide) attenuates intracellular T. gondii multiplication, confirmed by biotinylated PES binding directly to both host Hsp70 and TgHSP70 (verified by PES binding assay and molecular docking); silencing of host Hsp70 also reduces parasite multiplication, with attenuation linked to disruption of host autophagy. Pharmacological inhibition (PES), biotinylated PES binding assay, host Hsp70 siRNA knockdown, molecular docking (TgHsp70 structural analysis), autophagy functional assay Biochimica et biophysica acta. Molecular cell research Medium 33157166
2000 Immune factors (IFN-γ, TNF-α, reactive nitrogen intermediates) do not play primary roles in inducing TgHSP70 production in vivo: virulent RH strain tachyzoites from nude, SCID, IFN-γ receptor KO, and TNF receptor KO mice all produced similar levels of HSP70 as immunocompetent mice. Western blot analysis of HSP70 in tachyzoites recovered from immunodeficient mice (nude, SCID, IFN-γR KO, TNFR KO) International journal for parasitology Medium 11428337
2014 Systemic (serum) detection of TgHSP70 protein depends on parasite killing by the host immune response, while increased TgHSP70 expression in the brain correlates with parasite multiplication rate; dexamethasone-induced immunosuppression decreased systemic TgHSP70 while increasing cerebral parasitism and TgHSP70 brain expression. ELISA (serum TgHSP70 and antibody levels), immunohistochemistry (brain TgHSP70), immune complex detection, dexamethasone immunosuppression model, comparison of BALB/c vs C57BL/6 mice PloS one Low 24801069
2023 TgHSP70 directly binds TLR4 (demonstrated by molecular docking, localized surface plasmon resonance, and co-immunoprecipitation), and this interaction activates TLR4/NF-κB signaling; coixol disrupts TgHSP70-TLR4 interaction and inhibits downstream iNOS, TNF-α, and HMGB1 overproduction. Molecular docking, localized surface plasmon resonance (LSPR), co-immunoprecipitation, ELISA, Western blot, immunofluorescence, qPCR International immunopharmacology Medium 36933491
2000 The carboxy-terminal region of TgHSP70 mediates its immunosuppressive/deleterious effect on host protective immunity: immunization with rTgHSP70-full-length or rTgHSP70-C-terminal region increased brain parasite burden after infection, while rTgHSP70-N-terminal region did not. Immunization with recombinant protein fragments, quantitative competitive PCR (QC-PCR) for brain parasite load (SAG1 gene) The Korean journal of parasitology Low 10905074
2019 Inducible Hsp70 expressed on the membrane of T. gondii-infected dendritic cells and macrophages triggers Hsp70-dependent autophagy in CD40-expressing endothelial cells via beclin 1 and ULK1, restricting T. gondii invasion of neural tissue; this anti-parasitic activity required both CD40 expression in endothelial cells and inducible Hsp70 expression in the infecting leukocytes. In vivo infection model (retina and brain parasite load), adoptive transfer of infected monocytes/DCs, genetic knockouts (beclin 1, ULK1), autophagy assay, anti-Hsp70 functional blocking Infection and immunity Medium 31109947
2024 When bag1 (HSP30) is knocked out in T. gondii ME49, transcription of HSP70 (along with HSP20, HSP21, HSP40, HSP60, HSP90, and BFD1) is significantly upregulated during early bradyzoite differentiation, indicating that HSP70 participates in a compensatory stress-response network that partially substitutes for BAG1 function in cyst formation. CRISPR/Cas9 gene knockout, qPCR (transcriptional analysis of HSP family members), Western blot, in vitro differentiation assay, mouse infection model Parasites & vectors Low 39080770

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Bradyzoite development in Toxoplasma gondii and the hsp70 stress response. Infection and immunity 104 9632598
2002 Heat shock protein 70 is a potential virulence factor in murine toxoplasma infection via immunomodulation of host NF-kappa B and nitric oxide. Journal of immunology (Baltimore, Md. : 1950) 91 12097402
2011 Intracellular protozoan parasites of humans: the role of molecular chaperones in development and pathogenesis. Protein and peptide letters 90 20955165
2003 Induction of protective immunity by DNA vaccination with Toxoplasma gondii HSP70, HSP30 and SAG1 genes. Vaccine 76 12798627
2006 Toxoplasma gondii-derived heat shock protein 70 stimulates maturation of murine bone marrow-derived dendritic cells via Toll-like receptor 4. Cell stress & chaperones 55 16572725
1999 Role of Toxoplasma gondii HSP70 and Toxoplasma gondii HSP30/bag1 in antibody formation and prophylactic immunity in mice experimentally infected with Toxoplasma gondii. Microbiology and immunology 49 10449253
2000 Anti-HSP70 autoantibody formation by B-1 cells in Toxoplasma gondii-infected mice. Infection and immunity 47 10948102
2005 Toll-like receptor 4 mediates tolerance in macrophages stimulated with Toxoplasma gondii-derived heat shock protein 70. Infection and immunity 46 16040976
2002 Toxoplasma gondii-derived heat shock protein HSP70 functions as a B cell mitogen. Cell stress & chaperones 43 12653480
2000 Toxoplasma gondii Hsp70 as a danger signal in toxoplasma gondii-infected mice. Cell stress & chaperones 43 11048655
2004 Toxoplasma gondii infection inhibits the development of lupus-like syndrome in autoimmune (New Zealand Black x New Zealand White) F1 mice. International immunology 39 15148287
1998 Expression of Toxoplasma gondii-specific heat shock protein 70 during In vivo conversion of bradyzoites to tachyzoites. Infection and immunity 37 9673286
2005 Identification and characterization of cross-reactive antigens from Neospora caninum and Toxoplasma gondii. Parasitology 36 15991490
2002 Roles of IFN-gamma on stage conversion of an obligate intracellular protozoan parasite, Toxoplasma gondii. International reviews of immunology 36 12486821
1998 Gene sequence and transcription differences in 70 kDa heat shock protein correlate with murine virulence of Toxoplasma gondii. International journal for parasitology 32 9724875
2002 Involvement of MyD88 in host defense and the down-regulation of anti-heat shock protein 70 autoantibody formation by MyD88 in Toxoplasma gondii-infected mice. The Journal of parasitology 31 12435148
1995 Heat shock proteins of Toxoplasma gondii. Parasite immunology 31 8552407
2017 Recombinant TgHSP70 Immunization Protects against Toxoplasma gondii Brain Cyst Formation by Enhancing Inducible Nitric Oxide Expression. Frontiers in cellular and infection microbiology 29 28487847
2003 The role of anti-HSP70 autoantibody-forming V(H)1-J(H)1 B-1 cells in Toxoplasma gondii-infected mice. International immunology 29 12502724
2011 Innate immunity in DNA vaccine with Toxoplasma gondii-heat shock protein 70 gene that induces DC activation and Th1 polarization. Vaccine 28 21236236
2017 Interleukin-17A-Deficient Mice Are Highly Susceptible to Toxoplasma gondii Infection Due to Excessively Induced T. gondii HSP70 and Interferon Gamma Production. Infection and immunity 25 28893913
2010 Toxoplasma gondii infection inhibits the mitochondrial apoptosis through induction of Bcl-2 and HSP70. Parasitology research 25 20680337
2007 Molecular phylogenetic analysis in Hammondia-like organisms based on partial Hsp70 coding sequences. Parasitology 25 17462122
2023 Coixol ameliorates Toxoplasma gondii infection-induced lung injury by interfering with T. gondii HSP70/TLR4/NF-κB signaling pathway. International immunopharmacology 22 36933491
2008 Toxoplasma gondii-derived heat shock protein 70 induces lethal anaphylactic reaction through activation of cytosolic phospholipase A2 and platelet-activating factor via Toll-like receptor 4/myeloid differentiation factor 88. Microbiology and immunology 22 18667035
2004 Identification and characterisation of a regulatory region in the Toxoplasma gondii hsp70 genomic locus. International journal for parasitology 22 15003494
2012 Toxoplasma gondii antigens recognized by IgG antibodies differ between mice with and without active proliferation of tachyzoites in the brain during the chronic stage of infection. Infection and immunity 21 22851753
2004 Toxoplasma gondii-derived heat shock protein 70 stimulates the maturation of human monocyte-derived dendritic cells. Biochemical and biophysical research communications 21 15336548
2014 Natural killer cell intrinsic toll-like receptor MyD88 signaling contributes to IL-12-dependent IFN-γ production by mice during infection with Toxoplasma gondii. International journal for parasitology 19 24727091
2014 CTL induction by DNA vaccine with Toxoplasma gondii-HSP70 gene. Parasitology international 16 24448159
2014 Toxoplasma gondii 70 kDa heat shock protein: systemic detection is associated with the death of the parasites by the immune response and its increased expression in the brain is associated with parasite replication. PloS one 16 24801069
2004 Roles of Toxoplasma gondii-derived heat shock protein 70 in host defense against T. gondii infection. Microbiology and immunology 16 15557751
2011 Toxoplasma gondii Sis1-like J-domain protein is a cytosolic chaperone associated to HSP90/HSP70 complex. International journal of biological macromolecules 15 22209934
2020 Molecular chaperone function of stress inducible Hsp70 is critical for intracellular multiplication of Toxoplasma gondii. Biochimica et biophysica acta. Molecular cell research 14 33157166
2010 Protective immunity against lethal anaphylactic reaction in Toxoplasma gondii-infected mice by DNA vaccination with T. gondii-derived heat shock protein 70 gene. Parasitology international 14 20346412
2022 Resveratrol inhibits Toxoplasma gondii-induced lung injury, inflammatory cascade and evidences of its mechanism of action. Phytomedicine : international journal of phytotherapy and phytopharmacology 11 36332392
2020 iTRAQ-based Quantitative Proteomics Analysis Identifies Host Pathways Modulated during Toxoplasma gondii Infection in Swine. Microorganisms 11 32260483
2019 CD40 in Endothelial Cells Restricts Neural Tissue Invasion by Toxoplasma gondii. Infection and immunity 11 31109947
2016 Ginseng Stem-and-Leaf Saponin (GSLS)-Enhanced Protective Immune Responses Induced by Toxoplasma gondii Heat Shocked Protein 70 (HSP70) Against Toxoplasmosis in Mice. The Journal of parasitology 11 27828760
2006 Anaphylactic reaction induced by Toxoplasma gondii-derived heat shock protein 70. International immunology 11 16943259
2000 The production of a 70 kDa heat shock protein by Toxoplasma gondii RH strain in immunocompromised mice. International journal for parasitology 11 11428337
2004 A quantitative assay method of Toxoplasma gondii HSP70 mRNA by quantitative competitive-reverse transcriptase-PCR. Parasitology international 10 14984835
2015 Targeting Heat Shock Proteins 60 and 70 of Toxoplasma gondii as a Potential Drug Target: In Silico Approach. Interdisciplinary sciences, computational life sciences 9 26297309
2023 Protective effect of arctiin against Toxoplasma gondii HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of cytosolic phospholipase A2 and platelet-activating factor. International immunopharmacology 7 37995571
2021 Autoantibodies Against Ubiquitous and Confined Antigens in Patients With Ocular, Neuro-Ophthalmic and Congenital Cerebral Toxoplasmosis. Frontiers in immunology 6 34054794
2000 A role of carboxy-terminal region of Toxoplasma gondii-heat shock protein 70 in enhancement of T. gondii infection in mice. The Korean journal of parasitology 6 10905074
2024 Coixol mitigates Toxoplasma gondii infection-induced liver injury by inhibiting the Toxoplasma gondii HSP70/TLR4/NF-κB signaling pathway in hepatic macrophages. Journal of ethnopharmacology 5 39147001
2000 Antigens expressed in feline enteroepithelial-stages parasites of Toxoplasma gondii. The Journal of veterinary medical science 5 11073080
2019 Use of immunological methods to the detection of toxoplasmosis and heat shock protein HSP70 in men. Journal of parasitic diseases : official organ of the Indian Society for Parasitology 4 31263328
2010 Contribution of anti-Hsp70.1 IgG antibody levels to the diagnostic certainty of clinically suspected ocular toxoplasmosis. Investigative ophthalmology & visual science 4 20554617
2003 Correlation between the avidity maturation of anti-HSP70 IgG autoantibody and recombination activating gene expressions in peripheral lymphoid tissues of Toxoplasma gondii-infected mice. Microbiology and immunology 4 12725292
2024 The emerging role of Toxoplasma gondii in periodontal diseases and underlying mechanisms. Frontiers in immunology 3 39430742
2024 Toxoplasma gondii bradyzoite-specific BAG1 is nonessential for cyst formation due to compensation by other heat-shock proteins. Parasites & vectors 3 39080770
2008 Apoptotic pulsed dendritic cells induce a protective immune response against Toxoplasma gondii. Parasite immunology 3 19067843
2023 Corrigendum to "Protective effect of arctiin against Toxoplasma gondii HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of cytosolic phospholipase A2 and platelet-activating factor" [Int. Immunopharmacol. 126 (2023) 111254]. International immunopharmacology 2 38143162
2020 Prospective study of serum and aqueous humour anti-Hsp70.1 IgG antibody levels in ocular toxoplasmosis. Parasite immunology 2 32602946
2015 Isolation and characterization of Heat Shock Protein 100-Batu1 from Toxoplasma gondii RH strain. Experimental parasitology 1 25728232
2012 [Study on construction and immune protective effect of recombinant nucleic acid vaccine of Toxoplasma gondii]. Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control 1 22799162
2025 Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites. Pharmaceuticals (Basel, Switzerland) 0 39861113
2013 [Advances in genetyping of Toxoplasma gondii]. Zhongguo xue xi chong bing fang zhi za zhi = Chinese journal of schistosomiasis control 0 23894847