Immune response and immunopathology during toxoplasmosis

Dupont, Christian; Christian, David A.; Hunter, Christopher A.

doi:10.1007/s00281-012-0339-3

Cited by 298 publications

(297 citation statements)

References 264 publications

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“…Resistance to toxoplasmosis in the murine model relies on a potent Th1 axis driven by IL-12 production of IFN-γ (32,40), which acts to enhance several antimicrobial pathways in cells (Figure 2a). IFN-γ signaling mediated by STAT1 is essential for activating antitoxoplasmacidal activity in both hematopoietic and nonhematopoietic cells (128).…”

Section: Mechanisms Of Innate Resistancementioning

confidence: 99%

Genetic Mapping of Pathogenesis Determinants inToxoplasma gondii

Behnke

Dubey

Sibley

2016

Annu. Rev. Microbiol.

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Toxoplasma gondii is a widespread parasite of warm-blooded vertebrates that also causes opportunistic infections in humans. Rodents are a natural host for asexually replicating forms, whereas cats serve as the definitive host for sexual development. The laboratory mouse provides a model to study pathogenesis. Strains of T. gondii are globally diverse, with more than 16 distinct haplogroups clustered into 6 major clades. Forward genetic analysis of genetic crosses between different lineages has been used to define the molecular basis of acute virulence in the mouse. These studies have identified a family of secretory serine/threonine rhoptry kinases that target innate immune pathways to protect intracellular parasites from destruction. Rhoptry kinases target immunity-related GTPases, a family of immune effectors that is expanded in rodents. Similar forward genetic studies may be useful to define the basis of pathogenesis in other hosts, including humans, where infections of different strains present with variable clinical severity.

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Section: Mechanisms Of Innate Resistancementioning

confidence: 99%

Genetic Mapping of Pathogenesis Determinants inToxoplasma gondii

Behnke

Dubey

Sibley

2016

Annu. Rev. Microbiol.

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“…The disease is effectively controlled by the host immune response and remains dormant in the host neural and muscle tissues for the lifetime of the host (Dupont et al 2012). Although most individuals do not experience any symptoms, individuals with compromised immune system suffer a life-threatening disease.…”

Section: Introductionmentioning

confidence: 99%

Effect of Nigella sativa oil on experimental toxoplasmosis

2015

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Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii protozoon. It is most commonly treated by pyrimethamine (PYR); however, this was intolerable by many patients. The aim of this study was to assess therapeutic effects of Nigella sativa oil (NSO) alone and combined with pyrimethamine (PYR) compared to a previous combination of clindamycin (CLN) and (PYR). One hundred Albino mice were used in the current study and were equally divided into five groups: normal (I), infected untreated control (II); infected, treated with NSO-only (III); infected, treated with NSO + PYR (IV); and infected, treated with CLN + PYR (V). The virulent RH Toxoplasma strain was used in infection survival rates estimation, impression smears from liver and spleen, and histopathological and ultrastructural studies were done. Liver malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined. Interferon-γ and specific IgM were also measured in sera by ELISA. Results showed that NSO alone has no direct anti-Toxoplasma effect, whereas its combination with PYR produced potent effect that is comparable to CLN + PYR. It significantly increased the survival rate and decreased the parasite density and pathological insult in both liver and spleen. Also, significant increase in interferon-γ level denotes stimulation of cellular immunity. NSO + PYR combination markedly improved the antioxidant capacity of Toxoplasma infected mice compared to the infected untreated ones and to CLN/PYR. In conclusion, although NSO, if administered alone, has significant immunostimulant and antioxidant properties, it failed to decrease tachyzoite counts. Combination of NSO and PYR had synergistic effect in treatment of toxoplasmosis.

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“…Immunization with T. gondii extracts or killed noninvasive parasites also fails to elicit significant immunity to reinfection with T. gondii (10,11). Suboptimal vaccine priming using antigen-based vaccine formulations is not surprising in view of the requirement for populations of CD8 ϩ and CD4 ϩ T cells that produce the interferon gamma (IFN-␥) that is necessary to establish immunity and control of natural infection (12). In contrast to the suboptimal immunity elicited by antigen-based vaccines, immunization with whole transgenic organisms elicits potent Th1-biased immune responses associated with control of infection, and this vaccination strategy has enabled key experimental insights into host responses that prime immunity (13).…”

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confidence: 99%

Nonreplicating, Cyst-Defective Type II Toxoplasma gondii Vaccine Strains Stimulate Protective Immunity against Acute and Chronic Infection

Fox

Bzik

2015

Infect Immun

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Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II ⌬ku80 genetic background by targeting the deletion of the orotidine 5=-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of virulence in mice, and loss of the ability to develop cysts and chronic infection. Vaccination of mice using type II ⌬ku80 ⌬ompdc mutants stimulated a fully protective CD8؉ T celldependent immunity that prevented acute infection by type I and type II strains of T. gondii, and this vaccination also severely reduced or prevented cyst formation after type II challenge infection. Nonreverting, nonreplicating, and non-cyst-forming ⌬ompdc mutants provide new tools to examine protective immune responses elicited by vaccination with a live attenuated type II vaccine.T oxoplasma gondii is an obligate intracellular parasite with an extremely broad host range inclusive of most birds and virtually all mammals (1). T. gondii chronically infects approximately one-third of the human population (2). Three major strain types are found in North America and Europe, and these type I, II, or III strains differ with respect to their virulence traits in mice (3). Type I strains are considered to be highly virulent, type II strains have low virulence, and type III strains are considered to be avirulent. Following acute infection by type II strains of T. gondii, a chronic infection is established. Chronic infection is characterized by slow-growing bradyzoite forms within tissue cysts in brain, muscle, and eye (4), and infection is considered to be lifelong (5, 6). Reactivated infection during AIDS or immune suppression may cause a severe and difficult to treat toxoplasmic encephalitis (7) or recurrent ocular toxoplasmosis (8). Vaccination against Toxoplasma is difficult due to the existence of multiple antigenically distinct strain types and multiple antigenically distinct developmental stages. Toxoplasma also can effectively escape immunity by the development of a chronic encysted stage that is not easily cleared by immune responses.Antigen-based vaccine formulations provide only a partially protective immunity and do not prevent the establishment of tissue cysts and chronic infection following exposure to T. gondii (9). Immunization with T. gondii extracts or killed noninvasive parasites also fails to elicit significant immunity to reinfection with T. gondii (10, 11). Suboptimal vaccine priming using antigen-based vaccine formulations is not surprising in view of the requirement for populations of CD8 ϩ and CD4 ϩ T cells that produce the inter...

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Immune response and immunopathology during toxoplasmosis

Cited by 298 publications

References 264 publications

Genetic Mapping of Pathogenesis Determinants inToxoplasma gondii

Genetic Mapping of Pathogenesis Determinants inToxoplasma gondii

Effect of Nigella sativa oil on experimental toxoplasmosis

Nonreplicating, Cyst-Defective Type II Toxoplasma gondii Vaccine Strains Stimulate Protective Immunity against Acute and Chronic Infection

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