Role of IFN‐γ, TNF‐α, IL4 and IL 10 in the regulation of experimental <i>Toxoplasma gondii</i> infection.

Bessières, Marie-Hélène; Swierczynski, Béatrice; Cassaing, Sophie; Miédougé, Marcel; Ollé, Priscille; Segulela, Jean-Paul; Pipy, Bernard

doi:10.1111/j.1550-7408.1997.tb05800.x

Cited by 32 publications

(24 citation statements)

References 5 publications

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“…IFN‐γ production in response to intracellular microbial exposure is critical to the development of host protective immunity . Our results showed that high IFN‐γ production was induced by TgCyP in the experimental mice, which confirmed the hypothesis that CyP‐induced IL‐12 is important for the IFN‐γ production . Therefore, we can conclude that TgCyP can act as an IFN‐γ inducing factor and contribute to the control of toxoplasmosis.…”

Section: Discussionsupporting

confidence: 85%

“…However, pVAX1–TgCyP did not lead to a Th2‐type immune response in this study, as the production of IL‐4 and IL‐10 were maintained at the same levels among all the groups. IFN‐γ has been associated with a proliferation of T. gondii in macrophages . IFN‐γ production in response to intracellular microbial exposure is critical to the development of host protective immunity .…”

Section: Discussionmentioning

confidence: 99%

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The protective effect of aDNAvaccine encoding theToxoplasma gondiicyclophilin gene inBALB/cmice

Gong

Huang

et al. 2013

Parasite Immunology

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Toxoplasmosis is a world-wide zoonosis that causes significant public health and veterinary problems. The study of vaccines remains the most promising method for the future prevention and control of toxoplasmosis. Recombinant Toxoplasma gondii cyclophilin has been shown to have potent PPIase and IL-12-inducing activities, thus promoting the stabilization of T. gondii's life cycle and maintaining the survival of its host during evolution. In this study, the T. gondii cyclophilin gene was used to construct a DNA vaccine (pVAX1-TgCyP). The immune response and protective efficacy of the vaccine against T. gondii infection in BALB/c mice were evaluated. All BALB/c mice that were vaccinated with pVAX1-TgCyP developed a high response with TgCyP-specific antibodies, and significant splenocyte proliferation (P < 0·05) compared with pVAX1 vector and PBS groups. pVAX1-TgCyP also induced a significant Th1 type immune response, indicated by the higher production of IL-2 and IFN-γ (P < 0·05). The survival rate of BALB/c mice increased significantly after vaccination with pVAX1-TgCyP (37·5%) (P < 0·05). These results indicate that TgCyP is a highly efficacious vaccine candidate that can generate protective immunity against T. gondii infection in BALB/c mice.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

The protective effect of aDNAvaccine encoding theToxoplasma gondiicyclophilin gene inBALB/cmice

Gong

Huang

et al. 2013

Parasite Immunology

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“…IL-4 and IL-10 can promote the proliferation and differentiation of activated B cells, mast cells and peripheral lymphocytes and were showed to play an important role during the early phase of acute T. gondii infection [39,40], which partially contributed to protection against the acute stage of T. gondii infection in the present study. IL-23 secreted by activated macrophages and dendritic cells has been shown to enhance the production of the most critical cytokine, IFN-γ, in mediating host protection against T. gondii infection.…”

Section: Discussionmentioning

confidence: 77%

Protective immunity against Toxoplasma gondiiinduced by DNA immunization with the gene encoding a novel vaccine candidate: calcium-dependent protein kinase 3

et al. 2013

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BackgroundToxoplasma gondii can infect almost all warm-blood animals including human beings. The plant-like calcium-dependent protein kinases (CDPKs) harbored by T. gondii are involved in gliding motility, cell invasion, egress and some other developmental processes, and so have been implicated as important virulence factors.MethodsIn the present study, we constructed a DNA vaccine expressing T. gondii CDPK3 (TgCDPK3) and evaluated its protective efficacy against T. gondii infection in Kunming mice. The gene sequence encoding TgCDPK3 was inserted into the eukaryotic expression vector pVAX I, and mice were immunized with pVAX-CDPK3 intramuscularly.ResultsThe results showed that mice immunized with pVAX-CDPK3 developed a high level of specific antibodies and a strong lymphoproliferative response. The significantly increased levels of IFN-γ, IL-2, IL-12 (p70) and IL-23 and high ratio of IgG2a to IgG1 antibody titers indicated that a Th1 type response was elicited after immunization with pVAX-CDPK3. Furthermore, the percentage of CD4+ T cells in mice vaccinated with pVAX-CDPK3 was significantly increased. After lethal challenge with the tachyzoites of the virulent T. gondii RH strain, the mice immunized with pVAX-CDPK3 prolonged the survival time from 10 days to 24 days (13.5 ± 4.89) compared to untreated mice or those received PBS or pVAX I which died within 7 days (P < 0.05). In chronic infection model (10 cysts of the T. gondii PRU strain), the numbers of brain cysts of the mice immunized with pVAX-CDPK3 reduced significantly when compared with those in control groups (P < 0.05), and the rate of reduction could reach to about 50%.ConclusionsTgCDPK3 can generate protective immunity against acute and chronic T. gondii infection in Kunming mice and is a promising vaccine candidate for further development of an effective vaccine against T. gondii.

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“…Thus, the high ratio of IgG2a to IgG1 antibody titers and Th1-biased cytokine production [IFN-␥, IL-12(p70) and IL-2] indicated that the DNA vaccine is capable of stimulating Th1-dominated immune responses. Furthermore, IL-4 and IL-10 cytokines, associated with Th2 responses, have been shown to play important roles during the early phase of acute T. gondii infection (39). However, the low levels of IL-4 and IL-10 in the immunized mice compared with those in the controls may not promote sufficient mast cell responses and B-cell proliferation, consistent with the relatively low level of specific IgG antibodies.…”

Section: Rop18 (37) the Percentages Of Both Cd4mentioning

confidence: 71%

Evaluation of Immune Responses in Mice after DNA Immunization with Putative Toxoplasma gondii Calcium-Dependent Protein Kinase 5

Zhang

Huang

et al. 2014

Clin. Vaccine Immunol.

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dToxoplasma gondii can cause serious public health problems and economic losses worldwide. Calcium-dependent protein kinases (CDPKs) are key mediators of T. gondii signaling pathways and are implicated as important virulence factors. In the present study, we cloned a novel T. gondii CDPK gene, named TgCDPK5, and constructed the eukaryotic expression vector pVAX-CDPK5. Then, we evaluated the immune protection induced by pVAX-CDPK5 in Kunming mice. After injection of pVAX-CDPK5 intramuscularly, immune responses, determined with lymphoproliferative assays and cytokine and antibody measurements, were monitored, and mouse survival times and brain cyst formation were evaluated following challenges with the T. gondii RH strain (genotype I) and the PRU strain (genotype II). pVAX-CDPK5 effectively induced immune responses with increased specific antibodies, a predominance of IgG2a production, and a strong lymphocyte proliferative response. The levels of gamma interferon (IFN-␥), interleukin 2 (IL-2), and IL-12(p70) and the percentages of CD3 ؉ CD4 ؉ and CD3 ؉ CD8 ؉ cells in mice vaccinated with pVAX-CDPK5 were significantly increased. However, IL-4 and IL-10 were not produced in the vaccinated mice. These results demonstrate that pVAX-CDPK5 can elicit strong humoral and cellular Th1 immune responses. The survival time of immunized mice challenged with the T. gondii RH strain (8.67 ؎ 4.34 days) was slightly, but not significantly, longer than that in the control groups within 7 days (P > 0.05). The numbers of brain cysts in the mice in the pVAX-CDPK5 group were reduced by ϳ40% compared with those in the control groups (P < 0.05), which provides a foundation for the further development of effective subunit vaccines against T. gondii.

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Role of IFN‐γ, TNF‐α, IL4 and IL 10 in the regulation of experimental Toxoplasma gondii infection.

Cited by 32 publications

References 5 publications

The protective effect of aDNAvaccine encoding theToxoplasma gondiicyclophilin gene inBALB/cmice

The protective effect of aDNAvaccine encoding theToxoplasma gondiicyclophilin gene inBALB/cmice

Protective immunity against Toxoplasma gondiiinduced by DNA immunization with the gene encoding a novel vaccine candidate: calcium-dependent protein kinase 3

Evaluation of Immune Responses in Mice after DNA Immunization with Putative Toxoplasma gondii Calcium-Dependent Protein Kinase 5

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