immune-response

Strategies developed by Toxoplasma gondii to survive in the host

January 31, 2020
Zhu, W. B., Li, J. Y., Pappoe, F., Shen, J. L., Yu, L.
Frontiers in Microbiology 2019, 10

Click for abstract

One of the most successful intracellular parasites, Toxoplasma gondii has developed several strategies to avoid destruction by the host. These include approaches such as rapid and efficient cell invasion to avoid phagocytic engulfment, negative regulation of the canonical CD40-CD40L-mediated autophagy pathway, impairment of the noncanonical IFN-gamma-dependent autophagy pathway, and modulation of host cell survival and death to obtain lifelong parasite survival. Different virulent strains have even evolved different ways to cope with and evade destruction by the host. This review aims to illustrate every aspect of the game between the host and Toxoplasma during the process of infection. A better understanding of all aspects of the battle between Toxoplasma and its hosts will be useful for the development of better strategies and drugs to control the parasite.

Tagged: acute virulence, autophagy, autophagy proteins, cell invasion, dense granule protein, genetic-characterization, human-fibroblasts, immune evasion, immune-response, mironeme proteins, nitric oxide, Toxoplasma

Reviews

Disease tolerance in Toxoplasma infection

January 31, 2020
Melchor, S. J., Ewald, S. E.
Frontiers in Cellular and Infection Microbiology 2019, 9

Click for abstract

Toxoplasma gondii is a successful protozoan parasite that cycles between definitive fetid hosts and a broad range of intermediate hosts, including rodents and humans. Within intermediate hosts, this obligate intracellular parasite invades the small intestine, inducing an inflammatory response. Toxoplasma infects infiltrating immune cells, using them to spread systemically and reach tissues amenable to chronic infection. An intact immune system is necessary to control life-long chronic infection. Chronic infection is characterized by formation of parasite cysts, which are necessary for survival through the gastrointestinal tract of the next host. Thus, Toxoplasma must evade sterilizing immunity, but still rely on the host's immune response for survival and transmission. To do this, Toxoplasma exploits a central cost-benefit tradeoff in immunity: the need to escalate inflammation for pathogen clearance vs. the need to limit inflammation-induced bystander damage. What are the consequences of sustained inflammation on host biology? Many studies have focused on aspects of the immune response that directly target Toxoplasma growth and survival, commonly referred to as "resistance mechanisms." However, it is becoming clear that a parallel arm of the immune response has evolved to mitigate damage caused by the parasite directly (for example, egress-induced cell death) or bystander damage due to the inflammatory response (for example, reactive nitrogen species, degranulation). These so-called "disease tolerance" mechanisms promote tissue function and host survival without directly targeting the pathogen. Here we review changes to host metabolism, tissue structure, and immune function that point to disease tolerance mechanisms during Toxoplasma infection. We explore the impact tolerance programs have on the health of the host and parasite biolog

Tagged: chronic infection, gondii tachyzoites, ifn-gamma, immune-response, immunity, inferon gamma, innate, intracellural pathogen, natural-killer-cellsregulatory t- cells, oral infection, Parasite, resistancecachexia, small. intestine, tolerance, Toxoplasma gondii

Uncategorized

Chronic Toxoplasma gondii infection induces anti-N-methyl-D-aspartate receptor autoantibodies and associated behavioral changes and neuropathology

February 12, 2018
Li, Y, Viscidi, R. P., Kannan, G., McFarland,R., Pletnikov, M. V., Severance,E. G., Yolken, R. H., Xiao, J. C.
Infection and Immunity 2018; 86: DOI: 10.1128/iai.00398-18

Click for abstract

Anti-NMDA receptor (NMDAR) autoantibodies have been postulated to play a role in the pathogenesis of NMDAR hypofunction, which contributes to the etiology of psychotic symptoms. Toxoplasma gondii is a pathogen implicated in psychiatric disorders and associated with elevation of NMDAR autoantibodies. However, it remains unclear whether parasite infection is the cause of NMDAR autoantibodies. By using mouse models, we found that NMDAR autoantibody generation had a strong temporal association with tissue cyst formation, as determined by MAGI antibody seroreactivity (r = 0.96; P < 0.0001), which is a serologic marker for the cyst burden. The presence of MAGI antibody response, but not T. gondii IgG response, was required for NMDAR autoantibody production. The pathogenic relevance of NMDAR autoantibodies to behavioral abnormalities (blunted response to amphetamine-triggered activity and decreased locomotor activity and exploration) and reduced expression of synaptic proteins (the GLUN2B subtype of NMDAR and PSD-95) has been demonstrated in infected mice. Our study suggests that NMDAR autoantibodies are specifically induced by persistent T. gondii infection and are most likely triggered by tissue cysts. NMDAR autoantibody seroreactivity may be a novel pathological hallmark of chronic toxoplasmosis, which raises questions about NMDAR hypofunction and neurodegeneration in the infected brain.

Tagged: Amphetamine, antibodies, autoantibody, behavioral abnormalities, chronic infection, Dopamine, encephalitis, expression, gondii, hos, immune-response, MAGI antibody, mice, neuropathology, nmda receptor, tissue cyst, Toxoplasma gondii

Behavior Mental health

Latent toxoplasmosis is associated with neurocognitive impairment in young adults with and without chronic HIV infection

October 6, 2016
Ene, L., Marcotte, T. D., Umlauf, A., Grancea, C., Temereanca, A., Bharti, A., Achim, C. L., Letendre, S., Ruta, S. M.,
Journal of Neuroimmunology 2016; 299: 1-7.

Click for abstract

We evaluated the impact of latent toxoplasmosis (LT) on neurocognitive (NC) and neurobehavioural functioning in young adults with and without chronic HIV infection, using a standardised NC test battery, self-reported Beck Depression Inventory, Frontal System Behavior Scale, MINI-International Neuropsychiatric Interview and risk-assessment battery. 194 young adults (median age 24 years, 48.2% males) with chronic HIV infection (HIV +) since childhood and 51 HIV seronegative (HIV) participants were included. HIV + individuals had good current immunological status (median CD4: 479 cells/mu l) despite a low CD4 nadir (median: 93 cells/mu l). LT (positive anti-Toxoplasma IgG antibodies) was present in one third of participants. The impairment rates in the HIV with and without Toxo were not significantly different (p = 0.17). However, we observed an increasing trend (p < 0.001) in impairment rates with HIV and LT status: HIV -/LT- (6.1%); HIV -/LT+ (22%), HIV +/LT- (31%), HIV +/LT+ (49%). In a multi variable analysis using the entire study group there were main effects on cognition for HIV and also for LT. Within the HIV+ group LT was associated with worse performance globally (p = 0.006), in memory (p = 0.009), speed of information processing (p = 0.01), verbal (p = 0.02) and learning (p = 0.02) domains. LT was not associated with depressive symptoms, frontal systems dysfunction or risk behaviors in any of the groups. HIV participants with lower Toxoplasma antibody concentration had worse NC performance, with higher GDS values (p = 0.03) and worse learning (p = 0.002), memory (p = 0.006), speed of information processing (p = 0.01) T scores. Latent Toxoplasmosis may contribute to NC impairment in young adults, including those with and without chronic HIV infection.

Tagged: disorders, gondii antibody-titers, hiv, immune-response, individuals, latent toxoplasmosis, neurocognitive impairment, older-adults, risk, Schizophrenia, seropositivity, seroprevalence, suicide attempts, young adults

Cognitive functions

Neurobiological studies on the relationship between toxoplasmosis and neuropsychiatric diseases

October 9, 2015
Fabiani, S., Pinto, B., Bonuccelli, U., Bruschi, F.
Journal of the Neurological Sciences 2015; 35:3-8

Click for abstract

Toxoplasma gondii is a widespread protozoan parasite infecting approximately one third of the world population. After proliferation of tachyzoites during the acute stage, the parasite forms tissue cysts in various anatomical sites including the Central Nervous tissue, and establishes a chronic infection. Clinical spectrum normally ranges from a completely asymptomatic infection to severe multi-organ involvement. Many studies have suggested T. gondii infection as a risk factor for the development of some neuropsychiatric disorders, particularly schizophrenia. During the last years, a potential link with other neurobiological diseases such as Parkinson disease and Alzheimer disease has also been suggested. This review will focus on neurobiological and epidemiological data relating infection with T. gondii to neuropsychiatric diseases. (C) 2015 Elsevier B.V. All rights reserved.

Tagged: 1st-episode schizophrenia, brain, encephalitis, expression, gondii infection, immune-response, kynurenic acid, mechanisms, neurobiology, neurological diseases, neurotransmitter pathway, risk behavior, schizophrenia spectrum disorders, seroprevalence, t. gondii

Mental health

Gastroenterology issues in schizophrenia: Why the gut matters

May 28, 2015
Severance, E. G., Prandovszky, E., Castiglione, J., Yolken, R. H.
Current Psychiatry Reports 2015; 17: 10.1007/s11920-015-0574-0

Click for abstract

Genetic and environmental studies implicate immune pathologies in schizophrenia. The body's largest immune organ is the gastrointestinal (GI) tract. Historical associations of GI conditions with mental illnesses predate the introduction of antipsychotics. Cuirent studies of antipsychotic-naive patients support that gut dysfunction may be inherent to the schizophrenia disease process. Risk factors for schizophrenia (inflammation, food intolerances, Toxoplasma gondii exposure, cellular barrier defects) are part of biological pathways that intersect those operant in the gut. Central to GI function is a homeostatic microbial community, and early reports show that it is disrupted in schizophrenia. Bioactive and toxic products derived from digestion and microbial dysbiosis activate adaptive and innate immunity. Complement Clq, a brain-active systemic immune component, interacts with gut-related schizophrenia risk factors in clinical and experimental animal models. With accumulating evidence supporting newly discovered gut brain physiological pathways, treatments to ameliorate brain symptoms of schizophrenia should be supplemented with therapies to correct GI dysfunction.

Tagged: autism, autoimmunity, barrier function, blood brain barrier, celiac-disease, central-nervous-system, free diet, gastrointestinal inflammation, gluten, hospital admissions, immune-response, intestinal microbiota, microbiome, regulatory t-cells, relapsed schizophrenics, synapses

Mental health

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

October 10, 2013
Li, Y. Z., Weber, N. S., Fisher, J. A., Yolken, R. H., Cowan, D. N., Larsen, R. A., Niebuhr, D. W.
Schizophrenia Research 2013; 151: 36-42

Click for abstract

Introduction: Multiple studies have documented immune activation in many individuals with schizophrenia suggesting that antigens capable of generating a prolonged immune response may be important environmental factors in many cases of this disorder. While existing studies have found single-agent associations of antibodies to food and neurotropic infectious agents with schizophrenia, a simultaneous examination of multiple agents may shed light on agent interactions or possible etiopathogenic pathways. Methods: We used traditional regression and novel statistical techniques to examine associations of single and combined infectious and food antigens with schizophrenia. We tested 6106 serum samples from 855 cases and 1165 matched controls. Results: Higher antibody levels to casein were borderline significant in the prediction of schizophrenia (HR = 1.08,p = 0.06). Study participants with higher cytomegalovirus (CMV) lgG antibody levels had a reduced risk of developing schizophrenia (HR = 0.90; p = 0.02). While lgG antibodies to gliadin, Toxoplasma gondii, vaccinia, measles, and human herpesvirus-6 (HHV-6) showed no significant independent associations with schizophrenia, the increase in antibody levels to several combinations of agents, to include casein, measles, CMV, T gondii and vaccinia, was predictive of an 18-34% increase in the risk of developing schizophrenia. Conclusion: Certain patterns of antibodies, involving some agents, were predictive of developing schizophrenia, with the magnitude of association rising when the level of antibodies increased to two or more agents. A heightened antibody response to a combination of several infectious food antigens might be an indicator of an altered immune response to antigenic stimuli

Tagged: autoimmune diseases, biomarker, bipolar disorder, case-control, cerebrospinal fluid, cytomegalovirus, herpes-simplex, immune-response, psychosis, sero-epidemiology, serum-levels, t-cells, Toxoplasma gondii

Mental health

Neuropsychiatric disease and Toxoplasma gondii infection

October 26, 2009
Henriquez, S. A., Brett, R., Alexander, J., Pratt, J., Roberts, C. W.
Neuroimmunomodulation 2009; 16: 122-133.

Click for abstract

Toxoplasma gondii infects approximately 30% of the world's population, but causes overt clinical symptoms in only a small proportion of people. In recent years, the ability of the parasite to manipulate the behaviour of infected mice and rats and alter personality attributes of humans has been reported. Furthermore, a number of studies have now suggested T. gondii infection as a risk factor for the development of schizophrenia and depression in humans. As T. gondii forms cysts that are located in various anatomical sites including the brain during a chronic infection, it is well placed anatomically to mediate these effects directly. The T. gondii genome is known to contain 2 aromatic amino acid hydroxylases that potentially could directly affect dopamine and/or serotonin biosynthesis. However, stimulation of the immune response has also recently been associated with mood and behavioural alterations in humans, and compounds designed to alter mood, such as fluoxetine, have been demonstrated to alter aspects of immune function. Herein, the evidence for T.-gondii-induced behavioural changes relevant to schizophrenia and depression is reviewed. Potential mechanisms responsible for these changes in behaviour including the role of tryptophan metabolism and the hypothalamic-pituitary-adrenal axis are discussed. Copyright (C) 2009 S. Karger AG, Basel

Tagged: anterior cingulate cortex, cd4(+) t-cells, central-nervous-system, cytokine messenger-rna, hippocampal volume, ifn-gamma, immune-response, major depressive disorder, pituitary-adrenal axis, rattus-norvegicus

Mental health

Toxoplasma gondii & Human Phenotype

Compendium of Known Effects and Ongoing Research

immune-response

Strategies developed by Toxoplasma gondii to survive in the host

Disease tolerance in Toxoplasma infection

Chronic Toxoplasma gondii infection induces anti-N-methyl-D-aspartate receptor autoantibodies and associated behavioral changes and neuropathology

Latent toxoplasmosis is associated with neurocognitive impairment in young adults with and without chronic HIV infection

Neurobiological studies on the relationship between toxoplasmosis and neuropsychiatric diseases

Gastroenterology issues in schizophrenia: Why the gut matters

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Neuropsychiatric disease and Toxoplasma gondii infection