Depressed Natural Killer Cell Cytotoxicity against<i>Plasmodium falciparum</i>–Infected Erythrocytes during First Pregnancies

Bouyou-Akotet, Marielle Karine; Issifou, Saadou; Meye, Jean‐François; Kombila, Maryvonne; Ngou-Milama, Édouard; Luty, Adrian J. F.; Kremsner, Peter G.; Mavoungou, Elie

doi:10.1086/380646

Cited by 54 publications

(50 citation statements)

References 34 publications

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“…Reduced responses to MalAg during acute infection (22) in malaria-exposed pregnant women compared to those in nonpregnant women (7,8,23) have been reported, with cytokine responses to mitogens in some cases being relatively preserved (7,22,23). The mechanisms by which this outcome occurs are likely to be complex, perhaps involving parasite-induced cytokine dysregulation (2) and disruption of antigen presentation or dendritic cell function (34) and, in pregnant women, hormones (3,35). It will be necessary to perform intensive functional and mechanistic studies to identify the important players and their respective roles in malaria-associated immune modulation.…”

Section: Discussionmentioning

confidence: 99%

Hemozoin Differentially Regulates Proinflammatory Cytokine Production in Human Immunodeficiency Virus-Seropositive and -Seronegative Women with Placental Malaria

et al. 2004

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Pregnant women are at an increased risk for malarial infection. Plasmodium falciparum accumulates in the placenta and is associated with dysregulated immune function and poor birth outcomes. Malarial pigment (hemozoin) also accumulates in the placenta and may modulate local immune function. In this study, the impact of hemozoin on cytokine production by intervillous blood mononuclear cells from malaria-infected placentas was investigated. There was a dose-dependent, suppressive effect of hemozoin on production of gamma interferon (IFN-␥), with less of an effect on tumor necrosis factor alpha (TNF-␣) and interleukin-10, in human immunodeficiency virus-seronegative (HIV ؊ ) women. In contrast, IFN-␥ and TNF-␣ production tended to increase in HIV-seropositive women with increasing hemozoin levels. Production patterns of cytokines, especially IFN-␥ in HIV ؊ women, followed different trends as a function of parasite density and hemozoin level. The findings suggest that the influences of hemozoin accumulation and high-density parasitemia on placental cytokine production are not equivalent and may involve different mechanisms, all of which may operate differently in the context of HIV infection. Cytokine production dysregulated by accumulation of hemozoin or high-density parasitemia may induce pathology and impair protective immunity in HIV-infected and -uninfected women.

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Section: Discussionmentioning

confidence: 99%

Hemozoin Differentially Regulates Proinflammatory Cytokine Production in Human Immunodeficiency Virus-Seropositive and -Seronegative Women with Placental Malaria

et al. 2004

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“…However, as mentioned in that review, the main tool for assessing the cytolytic significance of NK cells in vivo has been mouse models. Interestingly, all but one publication found on NK cytotoxicity against human target cells infected with protozoa demonstrated increased NK cell cytotoxicity (8,9,27,30,32,41). The one negative report found, on Plasmodium (42), has been criticized for methodology in the context of NK cells (27).…”

Section: Vol 74 2006mentioning

confidence: 99%

The ProtozoanNeospora caninumDirectly Triggers Bovine NK Cells To Produce Gamma Interferon and To Kill Infected Fibroblasts

et al. 2006

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Natural killer (NK) cells are considered to be key players in the early innate responses to protozoan infections, primarily indirectly by producing gamma interferon (IFN-␥) in response to cytokines, like interleukin 12 (IL-12). We demonstrate that live, as well as heat-inactivated, tachyzoites of Neospora caninum, a Toxoplasma-like protozoan, directly trigger production of IFN-␥ from purified, IL-2-activated bovine NK cells. This response occurred independently of IL-12 but was increased by the addition of the cytokine. A similar IFN-␥ response was measured in cocultures of NK cells and N. caninum-infected autologous fibroblasts. However, no NK cell-derived IFN-␥ response was detected when cells were cultured with soluble antigens from the organism, indicating that intact tachyzoites or nonsoluble components are necessary for NK cell triggering. Furthermore, N. caninum-infected autologous fibroblasts had increased susceptibility to NK cell cytotoxicity compared to uninfected fibroblasts. This cytotoxicity was largely mediated by a perforin-mediated mechanism. The activating receptor NKp46 was involved in cytotoxicity against fibroblasts but could not explain the increased cytotoxicity against infected targets. Interestingly, N. caninum tachyzoites were able to infect cultured NK cells, in which tachyzoites proliferated inside parasitophorous vacuoles. Together, these findings underscore the role of NK cells as primary responders during a protozoan infection, describe intracellular protozoan infection of NK cells in vitro for the first time, and represent the first functional study of purified bovine NK cells in response to infection.

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“…The NK cell-mediated cytotoxicity against P. falciparum-infected erythrocytes in vitro was lower in samples obtained from primiparous women than in multiparous ones. 84 However, these findings were discussed and contested by Pearson. 85 He supported the "prolactin hypothesis" and pointed out that labor was not an appropriate time to assay for prolactin levels because they naturally fall 24 hours preceding the onset of delivery.…”

Section: Cortisol Prolactin and Susceptibility Of Pregnant Women To mentioning

confidence: 99%

Interactions Between Natural Killer Cells, Cortisol and Prolactin in Malaria During Pregnancy

Mavoungou¹

2006

Clinical Medicine & Research

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Natural killer cells derived from pluripotent hematopoietic stem cells are important cells of the immune system that have two main functions: a cytolytic activity and a cytokine-producing capacity. These functions are tightly regulated by numerous activating and inhibitory receptors, including newly discovered receptors that selectively trigger the cytolytic activity in a major histocompatibility complex independent manner. Based on their defining function of spontaneous cytotoxicity without prior immunization, natural killer (NK) cells have been thought to play a critical role in immune surveillance and cancer therapy. New insights into NK cell biology have suggested their major roles in the control of infections, particularly in Plasmodium falciparum infection and in fetal implantation. P. falciparum is the main protozoan parasite responsible for malaria causing 200-300 million clinical cases and killing over 3 million people each year. This review provides an update on NK cell function, ontogeny and biology in order to better understand the role of NK cells in pregnancy in regions where malaria is endemic. Understanding mechanisms of NK cell functions may lead to novel therapeutic strategies for the treatment of human disease, in general, and particularly in the fight against malaria.

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Depressed Natural Killer Cell Cytotoxicity againstPlasmodium falciparum–Infected Erythrocytes during First Pregnancies

Cited by 54 publications

References 34 publications

Hemozoin Differentially Regulates Proinflammatory Cytokine Production in Human Immunodeficiency Virus-Seropositive and -Seronegative Women with Placental Malaria

Hemozoin Differentially Regulates Proinflammatory Cytokine Production in Human Immunodeficiency Virus-Seropositive and -Seronegative Women with Placental Malaria

The ProtozoanNeospora caninumDirectly Triggers Bovine NK Cells To Produce Gamma Interferon and To Kill Infected Fibroblasts

Interactions Between Natural Killer Cells, Cortisol and Prolactin in Malaria During Pregnancy

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