Immunomodulatory Effects of Cold Stress on Mice Infected Intraperitoneally with a 50% Lethal Dose of Toxoplasma gondii

2001 ◽  
Vol 9 (1) ◽  
pp. 6-12 ◽  
Author(s):  
Hernan Aviles ◽  
Fernando P. Monroy
Keyword(s):  
Toxoplasma Gondii ◽  
Cold Stress ◽  
Lethal Dose ◽  
Immunomodulatory Effects

Toxoplasma gondii: Cold Stress-Induced Modulation of Antibody Responses

2001 ◽  
Vol 99 (2) ◽  
pp. 89-96 ◽  
Author(s):  
Hernan O. Aviles ◽  
Fernando P. Monroy
Keyword(s):  
Toxoplasma Gondii ◽  
Cold Stress ◽  
Antibody Responses

scholarly journals Nano DNA Vaccine Encoding Toxoplasma gondii Histone Deacetylase SIR2 Enhanced Protective Immunity in Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1582
Author(s):  
Zhengqing Yu ◽  
Yujia Lu ◽  
Wandi Cao ◽  
Muhammad Tahir Aleem ◽  
Junlong Liu ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Histone Deacetylase ◽  
Dna Vaccine ◽  
Laser Scanning ◽  
Lethal Dose ◽  
Parasite Burden ◽  
Effective Vaccine ◽  
Th2 Immune Response ◽  
Plga Nanospheres

The pathogen of toxoplasmosis, Toxoplasma gondii (T. gondii), is a zoonotic protozoon that can affect the health of warm-blooded animals including humans. Up to now, an effective vaccine with completely protection is still inaccessible. In this study, the DNA vaccine encoding T. gondii histone deacetylase SIR2 (pVAX1-SIR2) was constructed. To enhance the efficacy, chitosan and poly (d, l-lactic-co-glycolic)-acid (PLGA) were employed to design nanospheres loaded with the DNA vaccine, denoted as pVAX1-SIR2/CS and pVAX1-SIR2/PLGA nanospheres. The pVAX1-SIR2 plasmids were transfected into HEK 293-T cells, and the expression was evaluated by a laser scanning confocal microscopy. Then, the immune protections of pVAX1-SIR2 plasmid, pVAX1-SIR2/CS nanospheres, and pVAX1-SIR2/PLGA nanospheres were evaluated in a laboratory animal model. The in vivo findings indicated that pVAX1-SIR2/CS and pVAX1-SIR2/PLGA nanospheres could generate a mixed Th1/Th2 immune response, as indicated by the regulated production of antibodies and cytokines, the enhanced maturation and major histocompatibility complex (MHC) expression of dendritic cells (DCs), the induced splenocyte proliferation, and the increased percentages of CD4+ and CD8+ T lymphocytes. Furthermore, this enhanced immunity could obviously reduce the parasite burden in immunized animals through a lethal dose of T. gondii RH strain challenge. All these results propose that pVAX1-SIR2 plasmids entrapped in chitosan or PLGA nanospheres could be the promising vaccines against acute T. gondii infections and deserve further investigations.

Cold Stress-Induced Modulation of Cell Immunity during Acute Toxoplasma gondii Infection in Mice

1999 ◽  
Vol 85 (3) ◽  
pp. 442 ◽  
Author(s):  
Suman K. Banerjee ◽  
Hernan Aviles ◽  
Mary T. Fox ◽  
Fernando P. Monroy
Keyword(s):  
Toxoplasma Gondii ◽  
Cold Stress ◽  
Cell Immunity ◽  
Toxoplasma Gondii Infection

scholarly journals Effects of PERK eIF2α Kinase Inhibitor against Toxoplasma gondii

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Leonardo Augusto ◽  
Jennifer Martynowicz ◽  
Kirk A. Staschke ◽  
Ronald C. Wek ◽  
William J. Sullivan
Keyword(s):  
Endoplasmic Reticulum ◽  
Toxoplasma Gondii ◽  
Er Stress ◽  
Lethal Dose ◽  
Lytic Cycle ◽  
Host Cells ◽  
Initiation Factor ◽  
Α Subunit ◽  
Content Type ◽  
Eif2α Kinase

ABSTRACT Toxoplasma gondii is an obligate intracellular parasite that has infected one-third of the population. Upon infection of warm-blooded vertebrates, the replicating form of the parasite (tachyzoite) converts into a latent form (bradyzoite) present in tissue cysts. During immune deficiency, bradyzoites can reconvert into tachyzoites and cause life-threatening toxoplasmosis. We previously reported that translational control through phosphorylation of the α subunit of T. gondii eukaryotic initiation factor 2 (eIF2α) (TgIF2α) is a critical component of the parasite stress response. Diverse stresses can induce the conversion of tachyzoites to bradyzoites, including those disrupting the parasite's endoplasmic reticulum (ER) (ER stress). Toxoplasma possesses four eIF2α kinases, one of which (TgIF2K-A) localizes to the parasite ER analogously to protein kinase R-like endoplasmic reticulum kinase (PERK), the eIF2α kinase that responds to ER stress in mammalian cells. Here, we investigated the effects of a PERK inhibitor (PERKi) on Toxoplasma. Our results show that the PERKi GSK2606414 blocks the enzymatic activity of TgIF2K-A and reduces TgIF2α phosphorylation specifically in response to ER stress. PERKi also significantly impeded multiple steps of the tachyzoite lytic cycle and sharply lowered the frequency of bradyzoite differentiation in vitro. Pretreatment of host cells with PERKi prior to infection did not affect parasite infectivity, and PERKi still impaired parasite replication in host cells lacking PERK. In mice, PERKi conferred modest protection from a lethal dose of Toxoplasma. Our findings represent the first pharmacological evidence supporting TgIF2K-A as an attractive new target for the treatment of toxoplasmosis.

scholarly journals Toxoplasma Gondii Bradyzoites Form Spontaneously during Sporozoite-Initiated Development

1998 ◽  
Vol 66 (10) ◽  
pp. 4838-4844 ◽  
Author(s):  
M. E. Jerome ◽  
J. R. Radke ◽  
W. Bohne ◽  
D. S. Roos ◽  
M. W. White
Keyword(s):  
Toxoplasma Gondii ◽  
Lethal Dose ◽  
Alkaline Treatment ◽  
Host Cells ◽  
Specific Marker ◽  
Cell Type ◽  
Rate Of Growth ◽  
Infected Cells ◽  
Bradyzoite Differentiation ◽  
Sporozoite Infection

ABSTRACT Tachyzoites (VEG strain) that emerge from host cells infected withToxoplasma gondii sporozoites proliferate relatively fast and double their number every 6 h. This rate of growth is intrinsic, as neither the number of host cells invaded nor host cell type appears to influence emergent tachyzoite replication. Fast tachyzoite growth was not persistent, and following ∼20 divisions, the population uniformly shifted to slower growth. Parasites 10 days post-sporozoite infection doubled only once every 15 h and, unlike emergent tachyzoites, they grew at this slower rate over several months of continuous cell culture. The spontaneous change in tachyzoite growth rate preceded the expression of the bradyzoite-specific marker,BAG1. Within 24 h of the growth shift, 2% of the population expressed BAG1, and by 15 days post-sporozoite infection, 50% of the parasites were positive for this marker. Spontaneous BAG1 expression was not observed in sporozoites or in tachyzoites during fast growth (through day 6 post-sporozoite inoculation), although these tachyzoites could be induced to expressBAG1 earlier by culturing sporozoite-infected cells at pH 8.3. However, alkaline treatment also reduced the replication of emergent tachyzoites to the rate of growth-shifted parasites, supporting a link between reduced parasite growth and bradyzoite differentiation. The shift to slower growth was closely correlated with virulence in mice, as the initially fast-growing emergent tachyzoites were avirulent (100% lethal dose, >104 parasites), while a mutant VEG strain (MS-J) that is unable to growth shift caused 100% mortality in mice inoculated with 10 parasites. Parasites recovered from gamma interferon knockout mice inoculated with emergent tachyzoites grew at a slow rate and expressed BAG1, confirming that the replication switch occurs in animals and in the absence of a protective immune response.

scholarly journals Mucosal Administration of Recombinant Baculovirus Displaying Toxoplasma gondii ROP4 Confers Protection Against T. gondii Challenge Infection in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Keon-Woong Yoon ◽  
Ki-Back Chu ◽  
Hae-Ji Kang ◽  
Min-Ju Kim ◽  
Gi-Deok Eom ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Protective Efficacy ◽  
Lethal Dose ◽  
Recombinant Baculovirus ◽  
Oral Immunization ◽  
Challenge Infection ◽  
Antibody Responses ◽  
Physical Contact ◽  
Lethal Challenge ◽  
Iga Antibody

Pathogens require physical contact with the mucosal surface of the host organism to initiate infection and as such, vaccines eliciting both mucosal and systemic immune responses would be promising. Studies involving the use of recombinant baculoviruses (rBVs) as mucosal vaccines are severely lacking despite their inherently safe nature, especially against pathogens of global importance such as Toxoplasma gondii. Here, we generated rBVs displaying T. gondii rhoptry protein 4 (ROP4) and evaluated their protective efficacy in BALB/c mice following immunization via intranasal (IN) and oral routes. IN immunization with the ROP4-expressing rBVs elicited higher levels of parasite-specific IgA antibody responses compared to oral immunization. Upon challenge infection with a lethal dose of T. gondii ME49, IN immunization elicited significantly higher parasite-specific antibody responses in the mucosal tissues such as intestines, feces, vaginal samples, and brain than oral immunization. Marked increases in IgG and IgA antibody-secreting cell (ASC) responses were observed from intranasally immunized mice. IN immunization elicited significantly enhanced induction of CD4+, CD8+ T cells, and germinal center B (GC B) cell responses from secondary lymphoid organs while limiting the production of the inflammatory cytokines IFN-γ and IL-6 in the brain, all of which contributed to protecting mice against T. gondii lethal challenge infection. Our findings suggest that IN delivery of ROP4 rBVs induced better mucosal and systemic immunity against the lethal T. gondii challenge infection compared to oral immunization.

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