Changes in the Levels of Chemokines and Cytokines in the Placentas of Women with<i>Plasmodium falciparum</i>Malaria

Suguitan, Amorsolo L.; Leke, Rose G. F.; Fouda, Genevieve G.; Zhou, Ainong; Thuita, Lucy; Metenou, Simon; Fogako, Josephine; Megnekou, Rosette; Taylor, Diane Wallace

doi:10.1086/378500

Cited by 148 publications

(167 citation statements)

References 37 publications

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“…Infection of placenta by malaria parasites stimulate production of TNF-α [90][91][92][93] and IFN-γ [92,94], IL-1β [91] and IL-2 [92]. These cytokines induce T cell proliferation and enhance phagocytic activity of macrophages by production of reactive oxygen intermediates and nitric oxide [95].…”

Section: Specific Antimalarial Immunity During Pregnancymentioning

confidence: 99%

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Immune responses during gestational malaria: a review of the current knowledge and future trend of research

Maestre

Carmona‐Fonseca

2014

J Infect Dev Ctries

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Women pregnant with their first child are susceptible to severe P. falciparum disease from placental malaria because they lack immunity to placenta-specific cytoadherence proteins. In subsequent pregnancies, as immunity against placental parasites is acquired, there is a reduced risk of adverse effects of malaria on the mother and fetus and asymptomatic parasitaemia is common. In the case of vivax malaria, with increasing reports of severe cases in Asia and South America, the effects of infection by this species during pregnancy remain to be elucidated. This review summarized the main aspects involved in the acquisition of specific antimalarial immune responses during pregnancy with emphasis in research carried out in America and Asia, in order to offer a framework of interpretation for studies on pregnant women with malaria which are recently being produced in these regions. The authors conclude that (1) Effective humoral responses during gestational malaria are mainly directed against variant surface antigens codified by genes of the var2Csa family of P. falciparum; (2) Acquisition of immunity against these variant antigens depends on the degree and intensity of transmission, and the chance increases with age and successive pregnancies; (3) Antibody development is guided by specific cellular immune responses in cases of placental and maternal infection, and (4) The study of the significance of acquisition of specific immunity against both P. falciparum and P. vivax in America, should be performed.

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Section: Specific Antimalarial Immunity During Pregnancymentioning

confidence: 99%

“…The main source of IFN-γ in cases of gestational malaria are CD8+ T cells, CD4+ T cells, NK cells and the foetal trophoblast [90]. In general, increased levels of IFN-γ are associated with protection against gestational malaria [94].…”

Section: Specific Antimalarial Immunity During Pregnancymentioning

confidence: 99%

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

Maestre

Carmona‐Fonseca

2014

J Infect Dev Ctries

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“…There is no evidence for an effect of PM on TGF-b levels in maternal placental blood [26], but no study has analyzed the effect on T-cell-derived TGF-b production in cord blood. Studies suggest that CD8 1 T cells have suppressive activity in malaria exposed individuals [27,28], but no studies have investigated CD8 1 Treg in PM.…”

Section: Cd25mentioning

confidence: 99%

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth

et al. 2010

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Placental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign Ag. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analyzed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial Ag in utero results in the expansion of malaria-specific FOXP31 Treg and more generalized FOXP3 1 CD4 1 Treg in chronic and resolved PM, alongside increased Th1 pro-inflammatory responses (IFN-c, TNF-a, IFN-c:IL-10) in resolved PM infection only. These observations demonstrate a clear effect of exposure to malarial Ag in foetal life on the immune environment at birth, with a regulatory response dominating in the newborns with ongoing chronic PM, while those with resolved infection produce both regulatory and inflammatory responses. The findings might explain some of the adverse effects on the health of babies born to women with PM.

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“…First time mothers commonly suffer chronic PM characterized by inflammatory infiltrates in the intervillous spaces and increased levels of type I cytokines (4) and ␤ chemokines (5,6). The intervillous infiltrate consists primarily of macrophages with a smaller number of T cells, B cells, and granulocytes (7).…”

Section: P Lacental Malaria (Pm)mentioning

confidence: 99%

Genome-Wide Expression Analysis of Placental Malaria Reveals Features of Lymphoid Neogenesis during Chronic Infection

Muehlenbachs

Fried

Lachowitzer

et al. 2007

The Journal of Immunology

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Chronic inflammation during placental malaria (PM) is most frequent in first time mothers and is associated with poor maternal and fetal outcomes. In the first genome-wide analysis of the local human response to sequestered malaria parasites, we identified genes associated with chronic PM and then localized the corresponding proteins and immune cell subsets in placental cryosections. B cell-related genes were among the most highly up-regulated transcripts in inflamed tissue. The B cell chemoattractant CXCL13 was up-regulated >1,000-fold, and B cell-activating factor was also detected. Both proteins were expressed by intervillous macrophages. Ig L and H chain transcription increased significantly, and heavy depositions of IgG3 and IgM were observed in intervillous spaces. The B cell phenotype was heterogenous, including naive (CD27-negative), mature (CD138-positive), and cycling (Ki-67-positive) cells. B cells expressed T-bet but not Bcl-6, suggesting T cell-independent activation without germinal center formation. Genes for the Fc binding proteins Fc␥RIa, Fc␥RIIIa, and C1q were highly up-regulated, and the proteins localized to intervillous macrophages. Birth weight was inversely correlated with transcript levels of CXCL13, IgG H chain, and IgM H chain. The iron regulatory peptide hepcidin was also expressed but was not associated with maternal anemia. The results suggest that B cells and macrophages contribute to chronic PM in a process resembling lymphoid neogenesis. We propose a model where the production of Ig during chronic malaria may enhance inflammation by attracting and activating macrophages that, in turn, recruit B cells to further produce Ig in the intervillous spaces.

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Changes in the Levels of Chemokines and Cytokines in the Placentas of Women withPlasmodium falciparumMalaria

Cited by 148 publications

References 37 publications

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth

Genome-Wide Expression Analysis of Placental Malaria Reveals Features of Lymphoid Neogenesis during Chronic Infection

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