Pathogenesis of Malaria

Clark, Ian A.; Schofield, Louis

doi:10.1016/s0169-4758(00)01757-9

Cited by 88 publications

(55 citation statements)

References 39 publications

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“…PPAR␥ agonists down-regulate TNF-␣ and IL-6 and inhibit activation of inducible NO synthase in response to LPS and PMA (44 -45, 63). If the anti-inflammatory effects of PPAR␥ agonists can be demonstrated for malaria GPI-induced inflammation, then these compounds may decrease excessive induction of inflammatory cytokines implicated in the etiology of severe malaria (46). Here we show that PPAR␥-RXR agonists inhibit parasite-induced TNF-␣ secretion by monocytes and THP-1 cells.…”

Section: Figurementioning

confidence: 59%

“…Secretion of inflammatory cytokines during infection has been associated with a parasite-derived GPI toxin, which stimulates the release of TNF-␣, IL-1, and IL-6 from monocytes and M s. GPI from P. falciparum has also been shown to be a potent inducer of inducible NO synthase and NO output, presumably via the activation of transcription factors such as NF-B and c-rel (28,46). NO up-regulates ICAM-1 and VCAM-1 expression and has been implicated in the etiology of cerebral malaria (reviewed in Ref.…”

Section: Figurementioning

confidence: 99%

“…NO up-regulates ICAM-1 and VCAM-1 expression and has been implicated in the etiology of cerebral malaria (reviewed in Ref. 46). PPAR␥ agonists including 15d-PGJ 2 and thiazolidinediones have been reported to inhibit the induction of inflammatory genes via both PPAR␥-dependent and -independent mechanisms, an effect mediated, at least partially, by inhibition of NF-B (44 -45, 60 -63).…”

Section: Figurementioning

confidence: 99%

“…In addition, PPAR␥-RXR agonists have anti-inflammatory properties; down-regulating LPS and PMA induced proinflammatory cytokine secretion (44,45). If the anti-inflammatory effects of PPAR␥-RXR agonists can be extended to malaria-induced inflammation, then these compounds may be beneficial in decreasing the excessive or unbalanced secretion of proinflammatory cytokines implicated in severe malaria (46). We present evidence that PPAR␥-RXR agonist treatment results in an increase in CD36-mediated phagocytosis and a decrease in parasite-induced TNF-␣ secretion.…”

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confidence: 99%

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Peroxisome Proliferator-Activated Receptor γ-Retinoid X Receptor Agonists Increase CD36-Dependent Phagocytosis ofPlasmodium falciparum-Parasitized Erythrocytes and Decrease Malaria-Induced TNF-α Secretion by Monocytes/Macrophages

Serghides

Kain

2001

The Journal of Immunology

101

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Severe and fatal malaria is associated with the failure of host defenses to control parasite replication, excessive secretion of proinflammatory cytokines such as TNF-α, and sequestration of parasitized erythrocytes (PEs) in vital organs. The identification of CD36 as a major sequestration receptor has led to the assumption that it contributes to the pathophysiology of severe malaria and has prompted the development of antiadherence therapies to disrupt the CD36-PE interaction. This concept has been challenged by unexpected evidence that individuals deficient in CD36 are more susceptible to severe and cerebral malaria. In this study, we demonstrate that CD36 is the major receptor mediating nonopsonic phagocytosis of PEs by macrophages, a clearance mechanism of potential importance in nonimmune hosts at the greatest risk of severe malaria. CD36-mediated uptake of PEs occurs via a novel pathway that does not involve thrombospondin, the vitronectin receptor, or phosphatidylserine recognition. Furthermore, we show that proliferator-activated receptor γ-retinoid X receptor agonists induce an increase in CD36-mediated phagocytosis and a decrease in parasite-induced TNF-α secretion. Specific up-regulation of monocyte/macrophage CD36 may represent a novel therapeutic strategy to prevent or treat severe malaria.

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Section: Figurementioning

confidence: 59%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

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Peroxisome Proliferator-Activated Receptor γ-Retinoid X Receptor Agonists Increase CD36-Dependent Phagocytosis ofPlasmodium falciparum-Parasitized Erythrocytes and Decrease Malaria-Induced TNF-α Secretion by Monocytes/Macrophages

Serghides

Kain

2001

The Journal of Immunology

101

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“…Severe, life-threatening malaria caused by P. falciparum has been linked to the release of pro-inflammatory cytokines, especially tumour necrosis factor (TNF) [40][41][42][43]. The basis of adult susceptibility to severe disease caused by primary infection with P. falciparum may lie in the production of inordinately high levels of pro-inflammatory cytokines like TNF.…”

Section: Discussionmentioning

confidence: 99%

Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria

Baird¹,

Basri

Weina³

et al. 2003

Epidemiol. Infect.

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Migrants from Java arrive in hyperendemic Papua, Indonesia lacking exposure to endemic malaria. We evaluated records of evacuation to hospital with a diagnosis of severe malaria from a transmigration village in northeastern Papua. During the first 30 months, 198 residents with severe disease were evacuated (7·5 evacuations/100 person-years). During this period the risk of evacuation for adults (>15 years of age) was 2·8. (95% CI=2·1–3·8; P<0·0001) relative to children, despite apparently equal exposure to risk of infection. Relative risk (RR) for adults was greatest during the first 6 months (RR>16; 95% CI[ges ]2·0–129; P=0·0009), and diminished during the second 6 months (RR=9·4; 95% CI=2·7–32·8; P<0·0001) and the third 6 months (RR=3·7; 95% CI=1·7–7·9; P=0·0004). During the next two 6-month intervals, the RR for adults was 1·6 and 1·5 (95% CI range 0·8–2·6; P<0·18). Adults lacking chronic exposure were far more likely to progress to severe disease compared to children during initial exposure, but not after chronic exposure to infection.

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Carbohydrates and Immunology: Synthetic Oligosaccharide Antigens for Vaccine Formulation

2011

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Despite the enormous progress achieved by modern medicine, numerous diseases still have a profound impact on public health. Infectious diseases caused by a variety of microorganisms (viruses, fungi and parasites) and bacteria are a global major concern and, because of the emergence, for instance, of multidrug resistance, not only in developing countries. The development of preventative therapies, such as the rational design of novel and more efficient vaccines, might offer a solution to this state of affairs and other associated drawbacks. Vaccination is considered by the World Health Organization to be the most cost‐effective strategy for controlling infectious disease, because it should confer long‐term protective immunity in the population. A second consideration involves cancer. The outstanding progress achieved in the identification and structural characterization of tumour‐associated antigens has prompted their employment in tumour immunotherapy, on the basis of the observation that tumour cells possess specific antigens that can be recognized by an immune system appropriately conditioned to the task. Carbohydrates play key roles in many molecular recognition phenomena and they can affect any kind of interaction with the immune system. Saccharide‐based antigens (bacterial capsular polysaccharides or tumour‐associated carbohydrate antigens, for instance) have therefore been studied and employed in the formulation of vaccines. In recent years there has been increasing use of synthetic saccharide antigens for the formulation of vaccine candidates. These structures are indeed chemically well defined, devoid of biologic contaminants and, in principle, available in large amounts, relative to materials extracted from natural sources. In addition, synthetic saccharide antigens can also serve as haptens in protein conjugates, eliciting highly specific antibodies in animal models and humans. The great potential of synthetic saccharide antigens is attested to by the spectacular success of the Cuban vaccine against Haemophilus influenzae type b. Here we review the major advances in the development of synthetic carbohydrate‐based vaccines targeted against infectious diseases and cancer.

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Pathogenesis of Malaria

Cited by 88 publications

References 39 publications

Peroxisome Proliferator-Activated Receptor γ-Retinoid X Receptor Agonists Increase CD36-Dependent Phagocytosis ofPlasmodium falciparum-Parasitized Erythrocytes and Decrease Malaria-Induced TNF-α Secretion by Monocytes/Macrophages

Peroxisome Proliferator-Activated Receptor γ-Retinoid X Receptor Agonists Increase CD36-Dependent Phagocytosis ofPlasmodium falciparum-Parasitized Erythrocytes and Decrease Malaria-Induced TNF-α Secretion by Monocytes/Macrophages

Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria

Carbohydrates and Immunology: Synthetic Oligosaccharide Antigens for Vaccine Formulation

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