Reciprocal Regulation of Th1- and Th2-Cytokine-Producing T Cells during Clearance of Parasitemia in<i>Plasmodium falciparum</i>Malaria

Winkler, Stefan; Willheim, Martin; Baier, Karin; Schmid, Daniela; Aichelburg, Alexander; Graninger, Wolfgang; Kremsner, Peter G.

doi:10.1128/iai.66.12.6040-6044.1998

Cited by 79 publications

(46 citation statements)

References 33 publications

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“…120 Similarly, in humans, the absolute numbers of T cells markedly increased after treatment as opposed to levels observed during concurrent infection, suggesting malaria-induced lymphopenia. [121][122][123][124] Other studies found reduced numbers of T cells and natural killer cells in P. falciparum-infected individuals compared with the observed numbers when these individuals were healthy, 125,126 also suggestive of infection-induced lymphopenia.…”

Section: Loss Of Immune Cellsmentioning

confidence: 96%

Evaluating antidisease immunity to malaria and implications for vaccine design

Ademolue

Awandare

2017

Immunology

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SummaryImmunity to malaria could be categorized broadly as antiparasite or antidisease immunity. While most vaccine research efforts have focused on antiparasite immunity, the evidence from endemic populations suggest that antidisease immunity is an important component of natural immunity to malaria. The processes that mediate antidisease immunity have, however, attracted little to no attention, and most interests have been directed towards the antibody responses. This review evaluates the evidence for antidisease immunity in endemic areas and discusses the possible mechanisms responsible for it. Given the key role that inflammation plays in the pathogenesis of malaria, regulation of the inflammatory response appears to be a major mechanism for antidisease immunity in naturally exposed individuals.

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Section: Loss Of Immune Cellsmentioning

confidence: 96%

Evaluating antidisease immunity to malaria and implications for vaccine design

Ademolue

Awandare

2017

Immunology

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“…In children living in highly endemic areas, protection against P. falciparum correlates with the level of antigen‐specific proliferative responses 69 . It has been shown that a shift from a Th2 response to a more pronounced Th1 response is associated with the resolution of P. falciparum infection 70 . The precise role of effector CD4 T cells in protection of humans against malaria needs further investigation.…”

Section: Cell‐mediated Immunitymentioning

confidence: 99%

Immunity to asexual blood stage malaria and vaccine approaches

Wipasa

Elliott

et al. 2002

Immunol Cell Biol

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SummaryThe development of a malaria vaccine seems to be a definite possibility despite the fact that even individuals with a life time of endemic exposure do not develop sterile immunity. An effective malaria vaccine would be invaluable in preventing malaria-associated deaths in endemic areas, especially amongst children less than 5 years of age and pregnant women. This review discusses our current understanding of immunity against the asexual blood stage of malaria -the stage that is responsible for the symptoms of the disease -and approaches to the design of an asexual blood stage vaccine.Keywords: asexual blood stage, malaria, vaccine. Malaria and Plasmodium life cycleMalaria, a parasitic infection, is an important cause of mortality and morbidity in many parts of the world. Each year, an estimated 300-500 million people are affected worldwide. In reality, the true figure could be greater than three times this number. 1 Malaria kills 1-2 million people each year, mostly children under the age of 5 years and a significant number of pregnant women in sub-Saharan Africa. 2 It is a devastating infectious disease that not only affects the health system, but also slows the rate of long-term economic growth and development. The emergence of drug-resistant strains of the parasite has exacerbated the situation, and global climate change, disintegration of health services, human migration and population displacement have also contributed. 2 In recent years, there have also been more cases of malaria in travellers to endemic countries.Malaria is caused by unicellular protozoan parasites of the Plasmodium genus. 3 There are four species of malaria parasites that infect humans: P. falciparum, P. vivax, P. ovale and P. malariae. The most severe form of malaria is caused by P. falciparum. The severity of the disease depends largely on the species and strain of the infecting parasite, and the immunological status of the person who is infected.Cyclical fevers are the hallmark of malaria and typically occur shortly before or at the time of red blood cell (RBC) lysis as schizonts rupture to release new infectious merozoites (see below). This occurs every 48 h in P. vivax, P. ovale and P. falciparum, and every 72 h in P. malariae infection. Intense fever is accompanied by nausea, headaches and muscular pain, amongst other symptoms. In patients infected with P. vivax and P. ovale, relapse may recur months to years after initial infection. This is caused by re-activation of the silent liver-stage form of the parasites (hypnozoites). Renal failure, hypoglycaemia, hepatic dysfunction, severe anaemia, pulmonary oedema, convulsions and shock are complications in severe malaria. Cerebral malaria is a frequent presentation of severe P. falciparum infection and has been attributed in part to the unique ability of the parasites to alter the surface of infected RBC so that they bind to endothelial surfaces causing obstruction of cerebral blood flow. 4 Recent observations suggest that pro-inflammatory cytokines and nitric oxide induced by p...

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“…Redox-dependent cytokine modulation is especially relevant during the innate immune response when activated white blood cells, endothelial cells, and tissue parenchyma are exposed to different degrees of oxidative stress. Additionally, as malaria infection results in changes in the production of pro-and anti-inflammatory cytokines including interleukin (IL)-12, IL-6, tumor necrosis factor ␣ (TNF-␣), and IL-10 [13][14][15], it is possible that alterations in cytokine production in G6PD-deficient cells may contribute to the modulation of the inflammatory response to malaria. There is indirect evidence from human studies indicating that in vivo-or ex vivo-induced cytokine responses may be altered by G6PD deficiency in support of this hypothesis.…”

Section: Introductionmentioning

confidence: 99%

Augmented IL-10 production and redox-dependent signaling pathways in glucose-6-phosphate dehydrogenase-deficient mouse peritoneal macrophages

Wilmanski

Siddiqi²,

Deitch³

et al. 2005

Journal of Leukocyte Biology

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Glucose-6-phosphate dehydrogenase (G6PD) supports cellular antioxidant pathways. G6PD deficiency is associated with malaria protection but was shown to worsen the clinical course to injury. This study tested whether G6PD deficiency manifests in altered cytokine responses using peritoneal macrophages from a G6PD-deficient mouse model with a degree of defect similar to the common type A(-) human G6PD deficiency. Lipopolysaccharide (LPS)-induced interleukin (IL)-10 and IL-12 production was doubled in G6PD-deficient macrophages compared with wild-type (WT). Protein kinase C (PKC) activation by phorbol-ester prior to LPS resulted in a fivefold greater IL-10 production in G6PD-deficient macrophages compared with WT. Interferon-gamma treatment prior to LPS augmented IL-12 production in G6PD-deficient and WT macrophages and partially inhibited IL-10 production by G6PD-deficient macrophages. The antioxidants (N-acetyl-L-cysteine and glutathione ethyl-ester) blunted IL-10 and IL-12 production, indicating a role for oxidative stress in the observed response differences between deficient and WT macrophages. LPS-induced activation of nuclear factor-kappaB, cyclic adenosine monophosphate response element-binding protein, and specificity protein 3 was augmented in G6PD-deficient cells compared with WT. The PKCdelta inhibitor Rottlerin inhibited IL-10 and IL-12 production at different 50% effective-dose concentrations between deficient and WT macrophages, indicating elevated PKCdelta activity in deficient cells. This study reveals that activated G6PD-deficient macrophages display an augmented production of cytokines with a prominent impact on IL-10 production. The altered cytokine responses are associated with augmented activation of redox-dependent transcription factors and PKCdelta. Alterations in signaling pathways and associated changes in cytokine production may play a role in modulating the inflammatory responses following bacterial or malarial infections in G6PD deficiency.

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Reciprocal Regulation of Th1- and Th2-Cytokine-Producing T Cells during Clearance of Parasitemia inPlasmodium falciparumMalaria

Cited by 79 publications

References 33 publications

Evaluating antidisease immunity to malaria and implications for vaccine design

Evaluating antidisease immunity to malaria and implications for vaccine design

Immunity to asexual blood stage malaria and vaccine approaches

Augmented IL-10 production and redox-dependent signaling pathways in glucose-6-phosphate dehydrogenase-deficient mouse peritoneal macrophages

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