Toxoplasma gondii
            virus‐like particle vaccination alleviates inflammatory response in the brain upon
            T gondii
            infection

Abstract Background Infection with Toxoplasma gondii is thought to damage the brain and be a risk factor for neurological and psychotic disorders. The immune response-participating chemokine system has recently been considered vital for brain cell signaling and neural functioning. Here, we investigated the effect of the deficiency of C-C chemokine receptor 5 (CCR5), which is previously reported to be associated with T. gondii infection, on gene expression in the brain during T. gondii infection and the relationship between CCR5 and the inflammatory response against T. gondii infection in the brain. Results We performed a genome-wide comprehensive analysis of brain cells from wild-type and CCR5-deficient mice. Mouse primary brain cells infected with T. gondii were subjected to RNA sequencing. The expression levels of some genes, especially in astrocytes and microglia, were altered by CCR5-deficiency during T. gondii infection, and the gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed an enhanced immune response in the brain cells. The expression levels of genes which were highly differentially expressed in vitro were also investigated in the mouse brains during the T. gondii infections. Among the genes tested, only Saa3 (serum amyloid A3) showed partly CCR5-dependent upregulation during the acute infection phase. However, analysis of the subacute phase showed that in addition to Saa3, Hmox1 may also contribute to the protection and/or pathology partly via the CCR5 pathway. Conclusions Our results indicate that CCR5 is involved in T. gondii infection in the brain where it contributes to inflammatory responses and parasite elimination. We suggest that the inflammatory response by glial cells through CCR5 might be associated with neurological injury during T. gondii infection to some extent.

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Faculty Opinions recommendation of Intracranial injection of Gammagard, a human IVIg, modulates the inflammatory response of the brain and lowers Aβ in APP/PS1 mice along a different time course than anti-Aβ antibodies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718017780.793517527 ◽

2016 ◽

Author(s):

André Strydom

Keyword(s):

Inflammatory Response ◽

Time Course ◽

Intracranial Injection ◽

The Brain

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Brain Parasites and Suicide

Psychological Reports ◽

10.2466/12.13.pr0.107.5.424 ◽

2010 ◽

Vol 107 (2) ◽

pp. 424-424 ◽

Cited By ~ 19

Author(s):

David Lester

Keyword(s):

Toxoplasma Gondii ◽

Men And Women ◽

Suicide Rates ◽

The Brain

In a sample of 20 European nations, the prevalence of the brain parasite Toxoplasma gondii was positively associated with national suicide rates for men and women.

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Role of Purinergic Signalling in Endothelial Dysfunction and Thrombo-Inflammation in Ischaemic Stroke and Cerebral Small Vessel Disease

Biomolecules ◽

10.3390/biom11070994 ◽

2021 ◽

Vol 11 (7) ◽

pp. 994

Author(s):

Natasha Ting Lee ◽

Lin Kooi Ong ◽

Prajwal Gyawali ◽

Che Mohd Nasril Che Mohd Nassir ◽

Muzaimi Mustapha ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Dysfunction ◽

Inflammatory Response ◽

Small Vessel Disease ◽

Ischemia Reperfusion ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Purinergic Signalling ◽

Vessel Disease ◽

The Brain

The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood–brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.

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Insights into the molecular basis of host behaviour manipulation by Toxoplasma gondii infection

Emerging Topics in Life Sciences ◽

10.1042/etls20170108 ◽

2017 ◽

Vol 1 (6) ◽

pp. 563-572 ◽

Cited By ~ 1

Author(s):

Pierre-Mehdi Hammoudi ◽

Dominique Soldati-Favre

Keyword(s):

Toxoplasma Gondii ◽

Stress Responses ◽

Molecular Mechanisms ◽

Brain Regions ◽

Intermediate Hosts ◽

Toxoplasma Gondii Infection ◽

Host Parasite ◽

Host Behaviour ◽

The Brain ◽

Brain Homeostasis

Typically illustrating the ‘manipulation hypothesis’, Toxoplasma gondii is widely known to trigger sustainable behavioural changes during chronic infection of intermediate hosts to enhance transmission to its feline definitive hosts, ensuring survival and dissemination. During the chronic stage of infection in rodents, a variety of neurological dysfunctions have been unravelled and correlated with the loss of cat fear, among other phenotypic impacts. However, the underlying neurological alteration(s) driving these behavioural modifications is only partially understood, which makes it difficult to draw more than a correlation between T. gondii infection and changes in brain homeostasis. Moreover, it is barely known which among the brain regions governing fear and stress responses are preferentially affected during T. gondii infection. Studies aiming at an in-depth dissection of underlying molecular mechanisms occurring at the host and parasite levels will be discussed in this review. Addressing this reminiscent topic in the light of recent technical progress and new discoveries regarding fear response, olfaction and neuromodulator mechanisms could contribute to a better understanding of this complex host–parasite interaction.

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Integrative view of serpins in health and disease: the contribution of serpinA3

AJP Cell Physiology ◽

10.1152/ajpcell.00366.2020 ◽

2020 ◽

Author(s):

Andrea Sanchez-Navarro ◽

Isaac González-Soria ◽

Rebecca Caldiño-Bohn ◽

Norma A. Bobadilla

Keyword(s):

Oxidative Stress ◽

Inflammatory Response ◽

Cellular Processes ◽

Hormone Transport ◽

Integrative View ◽

Health And Disease ◽

The Brain ◽

Regulation Of Blood Pressure ◽

Common Function

Serpins are a superfamily of proteins characterized by their common function as serine protease inhibitors. So far, 36 serpins from nine clades have been identified. These proteins are expressed in all the organs and are involved in multiple important functions such as the regulation of blood pressure, hormone transport, insulin sensitivity, and the inflammatory response. Diseases such as obesity, diabetes, cardiovascular, and kidney disorders are intensively studied to find effective therapeutic targets. Given serpins' outstanding functionality, the deficiency or overexpression of certain types of serpin have been associated with diverse pathophysiological events. In particular, we will focus on reviewing the studies evaluating the participation of serpins, and particularly SerpinA3, in diverse diseases that occur in relevant organs such as the brain, retinas, corneas, lungs, cardiac vasculature, and kidneys. In this review, we summarize the role of serpins in physiological and pathophysiological processes, as well as recent evidence on the crucial role of SerpinA3 in several pathologies. Finally, we emphasize the importance of SerpinA3 in regulating cellular processes such as angiogenesis, apoptosis, fibrosis, oxidative stress, and the inflammatory response.

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Toxoplasma gondii injected neurons localize to the cortex and striatum and have altered firing

10.1101/2021.02.18.431839 ◽

2021 ◽

Author(s):

Oscar A. Mendez ◽

Emiliano Flores Machado ◽

Jing Lu ◽

Anita A. Koshy

Keyword(s):

Toxoplasma Gondii ◽

Single Neuron ◽

Latent Infection ◽

Ex Vivo ◽

Medium Spiny Neurons ◽

Patch Clamping ◽

Spiny Neurons ◽

The Brain ◽

Mapping Program

AbstractToxoplasma gondii is an intracellular parasite that causes a long-term latent infection of neurons. Using a custom MATLAB-based mapping program in combination with a mouse model that allows us to permanently mark neurons injected with parasite proteins, we found that Toxoplasma-injected neurons (TINs) are heterogeneously distributed in the brain, primarily localizing to the cortex followed by the striatum. Using immunofluorescence co-localization assays, we determined that cortical TINs are commonly (>50%) excitatory neurons (FoxP2+) and that striatal TINs are often (>65%) medium spiny neurons (MSNs) (FoxP2+). As MSNs have highly characterized electrophysiology, we used ex vivo slices from infected mice to perform single neuron patch-clamping on striatal TINs and neighboring uninfected MSNs (bystander MSNs). These studies demonstrated that TINs have highly abnormal electrophysiology, while the electrophysiology of bystander MSNs was akin to that of MSNs from uninfected mice. Collectively, these data offer new neuroanatomic and electrophysiologic insights into CNS toxoplasmosis.

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