Immunological reactions in response to apicomplexan glycosylphosphatidylinositols

Debierre‐Grockiego, Françoise; Schwarz, Ralph Τ.

doi:10.1093/glycob/cwq038

Cited by 57 publications

(46 citation statements)

References 95 publications

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“…Although the source of these transcripts in the placenta was not identified, it is noteworthy that this enzyme plays an important role in scavenging ROS extracellularly (41). In PM, where sequestered parasites (42) and responding immune cells (19, 20, 43) are likely to represent a potent source of ROS, extracellular SOD may be critical to counterbalance high levels of oxidative stress. Further studies will be required to determine the extent to which this particular enzyme may be a critical player in the response to PM, as well as cellular sources.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress: A Potential Therapeutic Target in Placental Malaria

et al. 2017

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Placental malaria, characterized by sequestration of Plasmodium falciparum in the maternal placental blood space and associated inflammatory damage, contributes to poor birth outcomes and ~200,000 infant deaths annually. Specific mechanisms that contribute to placental damage and dysfunction during malaria are not completely understood. To investigate a potential role for oxidative stress, antioxidant genes and markers for oxidative damage were assessed by quantitative PCR and immunohistochemistry in Plasmodium chabaudi AS-infected pregnant mice. Widespread evidence of lipid peroxidation was observed and was associated with higher antioxidant gene expression in conceptuses of infected mice. To assess the extent to which this oxidative damage might contribute to poor birth outcomes and be amenable to therapeutic intervention, infected pregnant mice were treated with N-acetylcysteine, a free radical scavenger, or tempol, an intracellular superoxide dismutase mimetic. The results show that mice treated with N-acetylcysteine experienced malaria induced–pregnancy loss at the same rate as control animals and failed to mitigate placental oxidative damage. In contrast, tempol-treated mice exhibited subtle improvement in embryo survival at gestation day 12. Although lipid peroxidation was not consistently reduced in the placentas of these mice, it was inversely related to embryo viability. Moreover, reduced IFN-γ and CCL2 plasma levels in treated mice were associated with midgestational embryo viability. Thus, although oxidative stress is remarkable in placental malaria and its mitigation by antioxidant therapy may improve pregnancy outcomes, the underlying mechanistic basis and potential therapeutic strategies require additional investigation.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress: A Potential Therapeutic Target in Placental Malaria

et al. 2017

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“…In addition, deletion of a bifunctional farnesyl diphosphate/ geranylgeranyl diphosphate synthase indicates that intracellular growth of T. gondii requires supplementation with farnesyl diphosphate or geranylgeranyl diphosphate from host cells (13). Lipids are energy sources and components of protozoa, but they are also involved in immune evasion and regulation of host metabolism and pathogenesis (14)(15)(16)(17). T. gondii are capable of regulating cell-signaling pathways through several virulent factors, such as kinases, phosphatases, and other enzymes, to subvert immune cells for their use as conduits for dissemination (10).…”

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confidence: 99%

Thioredoxin reductase fromToxoplasma gondii: an essential virulence effector with antioxidant function

et al. 2017

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Thioredoxin reductase (TR) can help pathogens resist oxidative-burst injury from host immune cells by maintaining a thioredoxin-reduction state during NADPH consumption. TR is a necessary virulence factor that enables the persistent infection of some parasites. We performed bioinformatics analyses and biochemical assays to characterize the activity, subcellular localization, and genetic ablation of Toxoplasma gondii TR (TgTR), to shed light on its biologic function. We expressed the TgTR protein with an Escherichia coli expression system and analyzed its enzyme activity, reporting a K m for the recombinant TgTR of 11.47-15.57 mM, using NADPH as a substrate, and 130.48-151.09 mM with dithio-bis-nitrobenzoic acid as a substrate. The TgTR sequence shared homology with that of TR, but lacked a selenocysteine residue in the C-terminal region and was thought to contain 2 flavin adenine dinucleotide (FAD) domains and 1 NADPH domain. In addition, immunoelectron microscopy results showed that TgTR was widely dispersed in the cytoplasm, and we observed that parasite antioxidant capacity, invasion efficiency, and proliferation were decreased in TR-knockout (TR-KO) strains in vitro, although this strain still stimulated the release of reactive oxygen species release in mouse macrophages while being more sensitive to H 2 O 2 toxicity in vitro. Furthermore, our in vivo results revealed that the survival time of mice infected with the TR-KO strain was significantly prolonged relative to that of mice infected with the wild-type strain. These results suggest that TgTR plays an important role in resistance to oxidative damage and can be considered a virulence factor associated with T. gondii

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“…Toxoplasma gondii is found worldwide, capable of infecting nucleated cells of many warm-blooded animals (McLeod et al, 2009; Debierre-Grockiego and Schwarz, 2010) and is estimated to infect half of the world's population (Liu et al, 2012). The disease burden for humans has been well-documented (McLeod et al, 2009).…”

Section: Exploiting Carbohydrate Antigens For Protozoan Parasite Vaccmentioning

confidence: 99%

Parasite Carbohydrate Vaccines

Jaurigue

Seeberger

2017

Front. Cell. Infect. Microbiol.

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Vaccination is an efficient means of combating infectious disease burden globally. However, routine vaccines for the world's major human parasitic diseases do not yet exist. Vaccines based on carbohydrate antigens are a viable option for parasite vaccine development, given the proven success of carbohydrate vaccines to combat bacterial infections. We will review the key components of carbohydrate vaccines that have remained largely consistent since their inception, and the success of bacterial carbohydrate vaccines. We will then explore the latest developments for both traditional and non-traditional carbohydrate vaccine approaches for three of the world's major protozoan parasitic diseases—malaria, toxoplasmosis, and leishmaniasis. The traditional prophylactic carbohydrate vaccine strategy is being explored for malaria. However, given that parasite disease biology is complex and often arises from host immune responses to parasite antigens, carbohydrate vaccines against deleterious immune responses in host-parasite interactions are also being explored. In particular, the highly abundant glycosylphosphatidylinositol molecules specific for Plasmodium, Toxoplasma, and Leishmania spp. are considered exploitable antigens for this non-traditional vaccine approach. Discussion will revolve around the application of these protozoan carbohydrate antigens for vaccines currently in preclinical development.

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Immunological reactions in response to apicomplexan glycosylphosphatidylinositols

Cited by 57 publications

References 95 publications

Oxidative Stress: A Potential Therapeutic Target in Placental Malaria

Oxidative Stress: A Potential Therapeutic Target in Placental Malaria

Thioredoxin reductase fromToxoplasma gondii: an essential virulence effector with antioxidant function

Parasite Carbohydrate Vaccines

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