The local immune response to intraocular Toxoplasma re-challenge: Less pathology and better parasite control through Treg/Th1/Th2 induction

Sauer, Arnaud; Rochet, E; Lahmar, I.; Brunet, Julie; Sabou, Marcela; Bourcier, Tristan; Candolfi, Ermanno; Pfaff, Alexander W.

doi:10.1016/j.ijpara.2013.04.004

Cited by 34 publications

(33 citation statements)

References 38 publications

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“…They also showed a deleterious TH17 response at the local level after primary infection which was reduced after reinfection. TH2/Treg responses were enhanced under the reinfection condition (35).…”

Section: Figmentioning

confidence: 96%

Role of CD4⁺Foxp3⁺Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii

2015

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Toxoplasmosis is caused by a protozoan parasite that infects humans and other warm-blooded animals. Infections in humans are generally asymptomatic, although immunosuppressed patients may exhibit severe symptoms. Similarly, primary infection during pregnancy can lead to miscarriage and neonatal malformations. Toxoplasmosis can be transmitted to humans via ingestion of oocysts or via the consumption of meat products contaminated with tissue cysts (1). Effective vaccination of domestic livestock can therefore prevent human infection with Toxoplasma gondii. It is possible to induce strong protection by immunization with a live attenuated strain (2). Live attenuated vaccine strain models are also useful for advancing the understanding of the protective host immune response (3-8). However, the information available about the mechanism of protection involved after vaccination with a type I attenuated strain was obtained with nonreplicating, nonpersistent strains, such as strains cps-1 (3-7) and ts4 (8). A strain known as Mic1.3KO was obtained in our laboratory by deleting the MIC1 and MIC3 genes (9). This strain was derived from the highly virulent type I RH strain, and its reduced invasion capacity in vitro was correlated with decreased virulence when injected into outbred Swiss OF1 mice (9). Type I strains are characterized by the rapid dissemination of the parasite and by a high parasite burden that results in death soon after infection by a single viable parasite in mice (10). High levels of gamma interferon (IFN-␥) were produced following infection with a type I parasite, and mice succumbed to uncontrolled parasite growth and associated inflammation (11,12). The Mic1.3KO strain with the MIC1 and MIC3 gene deletions showed reduced virulence, lower levels of dissemination throughout tissues, and lower levels of IFN-␥ production than the parental RH strain after injection into mice (13).In a model of lethal toxoplasmosis induced after oral administration of infection with a type II strain causing infection in C57BL/6 mice, overproduction of IFN-␥ was also responsible for mortality and was correlated with a sharp decline in the percentage of regulatory T cells (Tregs) just before death, supporting the hypothesis of defective immunoregulation (14). Tregs are a subpopulation of CD4 ϩ T cells, and their main function is to maintain immune homeostasis and tolerance (15). They constitutively express the interleukin-2 (IL-2) receptor alpha chain (IL2R␣), a surface receptor also known as CD25, and the intracellular fork head box-p3 transcription factor (Foxp-3) marker (16). The role of Tregs after infection with type II strains has been fully described (14,(17)(18)(19)(20)(21), and Tregs have been clearly implicated in the mortality of C57BL/6 mice after oral infection in the lethal ileitis model (14). The collapse of Tregs is correlated with pathogenicity and occurs only under highly pathogenic conditions since oral infection of BALB/c mice with a type II strain did not induce a reduction in the levels of Tregs (14). Howev...

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Section: Figmentioning

confidence: 96%

Role of CD4⁺Foxp3⁺Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii

2015

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“…Th17 cells are characterized by the production of IL-17 mediated by IL-23 from dendritic cells and probably may have both protective and proinflammatory effects. Different roles in infectious and inflammatory events are likely to be related to the local (cytokine) environment and the stage of the pathological process [20,21,22]. …”

Section: Pathophysiologymentioning

confidence: 99%

Ocular Toxoplasmosis: Recent Aspects of Pathophysiology and Clinical Implications

Pleyer

Schlüter

Mänz³

2014

Ophthalmic Res

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Toxoplasma gondii is an extremely successful opportunistic parasite which infects approximately one third of the human population worldwide. The impact of this parasite on human health becomes particularly manifest in congenital damage with infection and subsequent inflammation of neuronal tissues including the retina. Although advances in our understanding could be achieved in ocular toxoplasmosis, large gaps still exist on factors influencing the epidemiology and pathophysiology of this potentially blinding disease. We are only at the beginning of understanding the complex biology of this parasite and its mechanisms of invasion, virulence and interaction with the host's immune response. Since it is a preventable cause of blindness, it is necessary to assess factors that have the potential to control this disease in the future. This mini review will focus on recent advances in postnatal acquired ocular infection and the factors that may influence its prevalence and functional outcome.

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“…MMP-2 over-expression is observed in certain infections where eradication and control of immunopathogenesis rely on the development of protective type-2 responses (Oakley et al, 2013; Sauer et al, 2013). For instance, various parasites including plasmodium (Lima et al, 2012) and toxoplasma (Lu and Lai, 2013) species can trigger MMP-2 over-expression.…”

Section: Introductionmentioning

confidence: 99%

Activation of Toll-like Receptor-2 by Endogenous Matrix Metalloproteinase-2 Modulates Dendritic-Cell-Mediated Inflammatory Responses

et al. 2014

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SUMMARY Matrix metalloproteinase-2 (MMP-2) is involved in several physiological mechanisms, including wound healing and tumor progression. We show that MMP-2 directly stimulates dendritic cells (DCs) to both up-regulate OX40L on the cell surface and secrete inflammatory cytokines. The mechanism underlying DC activation includes physical association with Toll-like receptor-2 (TLR2), leading to NF-κB activation, OX40L up-regulation on DCs and ensuing TH2 differentiation. Significantly, MMP-2 polarizes T cells towards type-2 responses in vivo, in a TLR2-dependent manner. MMP-2-dependent type-2 polarization may represent a key immune regulatory mechanism to protect against a broad array of disorders, such as inflammatory, infectious and autoimmune diseases, which can be hijacked by tumors to evade immunity.

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The local immune response to intraocular Toxoplasma re-challenge: Less pathology and better parasite control through Treg/Th1/Th2 induction

Cited by 34 publications

References 38 publications

Role of CD4⁺Foxp3⁺Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii

Role of CD4⁺Foxp3⁺Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii

Ocular Toxoplasmosis: Recent Aspects of Pathophysiology and Clinical Implications

Activation of Toll-like Receptor-2 by Endogenous Matrix Metalloproteinase-2 Modulates Dendritic-Cell-Mediated Inflammatory Responses

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The local immune response to intraocular Toxoplasma re-challenge: Less pathology and better parasite control through Treg/Th1/Th2 induction

Cited by 34 publications

References 38 publications

Role of CD4+Foxp3+Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii

Role of CD4+Foxp3+Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii

Ocular Toxoplasmosis: Recent Aspects of Pathophysiology and Clinical Implications

Activation of Toll-like Receptor-2 by Endogenous Matrix Metalloproteinase-2 Modulates Dendritic-Cell-Mediated Inflammatory Responses

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Product

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Role of CD4⁺Foxp3⁺Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii

Role of CD4⁺Foxp3⁺Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii