<em>Toxoplasma</em> Immunomodulation Related to Neuropsychiatric Diseases

Toxoplasma gondii (T. gondii) causes toxoplasmic encephalitis resulting from reactivation of latent toxoplasmosis. It is the most frequent clinical manifestation, characterized by multiple necrotizing brain lesions. Bradyzoite tissue cysts activate an immune response that has a major impact on controlling parasite persistence in the brain. The immune mechanisms stimulated in the brain cause a local inflammatory mediated by Th1 immune reaction cytokines. Several studies have linked this process to that active during different neuropsychiatric disorders, such as Schizophrenia. In addition to the immune reaction activated in the brain, this latter has the capacity to stimulate neurotransmitter production. T. gondii induces high concentrations of dopamine and tyrosine hydroxylase in the central nervous system and has also been shown to increase kynurenine/tryptophan ratio and elevated Kynurenic acid level, mainly in astrocyte cells. This imbalance plays a role in the pathophysiology of Schizophrenia. Results of different studies explain in this chapter support the idea that Toxoplasma is an etiological factor in Schizophrenia

Current Knowledge on the Oxidative-Stress-Mediated Antimicrobial Properties of Metal-Based Nanoparticles

The emergence of multidrug-resistant (MDR) bacteria in recent years has been alarming and represents a major public health problem. The development of effective antimicrobial agents remains a key challenge. Nanotechnologies have provided opportunities for the use of nanomaterials as components in the development of antibacterial agents. Indeed, metal-based nanoparticles (NPs) show an effective role in targeting and killing bacteria via different mechanisms, such as attraction to the bacterial surface, destabilization of the bacterial cell wall and membrane, and the induction of a toxic mechanism mediated by a burst of oxidative stress (e.g., the production of reactive oxygen species (ROS)). Considering the lack of new antimicrobial drugs with novel mechanisms of action, the induction of oxidative stress represents a valuable and powerful antimicrobial strategy to fight MDR bacteria. Consequently, it is of particular interest to determine and precisely characterize whether NPs are able to induce oxidative stress in such bacteria. This highlights the particular interest that NPs represent for the development of future antibacterial drugs. Therefore, this review aims to provide an update on the latest advances in research focusing on the study and characterization of the induction of oxidative-stress-mediated antimicrobial mechanisms by metal-based NPs

Etude in vitrro de la réponse immunitaire inflammatoire au cours de l'encéphalite toxoplasmique humaine.

International audienc

Role of IFN-y in neuro-immune response during infection of human nervous cells by Toxoplasma gondii.

International audienc

Squalamine and Its Aminosterol Derivatives: Overview of Biological Effects and Mechanisms of Action of Compounds with Multiple Therapeutic Applications

International audienceSqualamine is a natural aminosterol that has been discovered in the tissues of the dogfish shark (Squalus acanthias). Studies have previously demonstrated that this promoter compound and its derivatives exhibit potent bactericidal activity against Gram-negative, Gram-positive bacteria, and multidrug-resistant bacteria. The antibacterial activity of squalamine was found to correlate with that of other antibiotics, such as colistin and polymyxins. Still, in the field of microbiology, evidence has shown that squalamine and its derivatives have antifungal activity, antiprotozoa effect against a limited list of protozoa, and could exhibit antiviral activity against both RNA- and DNA-enveloped viruses. Furthermore, squalamine and its derivatives have been identified as being antiangiogenic compounds in the case of several types of cancers and induce a potential positive effect in the case of other diseases such as experimental retinopathy and Parkinson’s disease. Given the diverse effects of the squalamine and its derivatives, in this review we provide the different advances in our understanding of the various effects of these promising molecules and try to draw up a non-exhaustive list of the different mechanisms of actions of squalamine and its derivatives on the human organism and on different pathogens

Infection of human nervous cells by different strains of Toxoplasma gondii in vitro: analysis of neuronal cytokine and chemokine expression profiles.

International audienc

Cinétique d'expression des cytokines et des chémokines lors d'une infection toxoplasmique cérébrale humaine in vitro.

International audienc

Interferon gamma effect on immune mediator production in human nerve cells infected by two strains of Toxoplasma gondii.

International audienceInterferon gamma (IFN-γ) is the major immune mediator that prevents toxoplasmic encephalitis in murine models. The lack of IFN-γ secretion causes reactivation of latent T. gondii infection that may confer a risk for severe toxoplasmic encephalitis. We analyse the effect of IFN-γ on immune mediator production and parasite multiplication in human nerve cells infected by tachyzoites of two T. gondii strains (RH and PRU). IFN-γ decreased the synthesis of MCP-1, G-CSF, GM-CSF and Serpin E1 in all cell types. It decreased IL-6, migration inhibitory factor (MIF) and GROα synthesis only in endothelial cells, while it increased sICAM and Serpin E1 synthesis only in neurons. The PRU strain burden increased in all nerve cells and in contrast, RH strain replication was controlled in IFN-γ-stimulated microglial and endothelial cells but not in IFN-γ-stimulated neurons. The proliferation of the PRU strain in all stimulated cells could be a specific effect of this strain on the host cell

Toxoplasma gondii Modulates the Host Cell Responses: An Overview of Apoptosis Pathways

Infection with Toxoplasma gondii has a major implication in public health. Toxoplasma gondii is an obligate intracellular protozoan parasite that can infect all nucleated cells belonging to a wide range of host species. One of the particularities of this parasite is its invasion and persistence in host cells of immunocompetent people. This infection is usually asymptomatic. In immunocompromised patients, the infection is severe and symptomatic. The mechanisms by which T. gondii persists are poorly studied in humans. In mouse models, many aspects of the interaction between the parasite and the host cells are being studied. Apoptosis is one of these mechanisms that could be modulated by Toxoplasma to persist in host cells. Indeed, Toxoplasma has often been implicated in the regulation of apoptosis and viability mechanisms in both human and murine infection models. Several of these studies centered on the regulation of apoptosis pathways have revealed interference of this parasite with host cell immunity, cell signalling, and invasion mechanisms. This review provides an overview of recent studies concerning the effect of Toxoplasma on different apoptotic pathways in infected host cells

Plant-Derived Antimicrobial Peptides as Potential Antiviral Agents in Systemic Viral Infections

International audienceNumerous studies have led to a better understanding of the mechanisms of action of viruses in systemic infections for the development of prevention strategies and very promising antiviral therapies. Viruses still remain one of the main causes of human diseases, mainly because the development of new vaccines is usually challenging and drug resistance has become an increasing concern in recent decades. Therefore, the development of potential antiviral agents remains crucial and is an unmet clinical need. One abundant source of potential therapeutic molecules are plants: they biosynthesize a myriad of compounds, including peptides which can have antimicrobial activity. Our objective is to summarize the literature on peptides with antiviral properties derived from plants and to identify key features of these peptides and their application in systemic viral infections. This literature review highlights studies including clinical trials which demonstrated that plant cyclotides have the ability to inhibit the growth of viruses causing human diseases, defensin-like peptides possess anti-HIV-1 activity, and lipid transfer proteins and some lectins exhibit a varied antimicrobial profile. To conclude, plant peptides remain interesting to explore in the context of emerging and re-emerging infectious diseases