Monocyte dysregulation and systemic inflammation during pediatric falciparum malaria

Dobbs, Katherine R.; Embury, Paula; Vulule, John; Odada, Peter Sumba; Rosa, Bruce A.; Mitreva, Makedonka; Kazura, James W.; Dent, Arlene E.

doi:10.1172/jci.insight.95352

Cited by 58 publications

(71 citation statements)

References 80 publications

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“…There are several studies on immune activation and inflammation during P. falciparum infection, and some of these have also examined T-cells, monocytes/macrophages and neutrophils [9][10][11][12], but the role of these cells during falciparum malaria are far from clear. In particular, most studies have focused on one of these cell subsets, and fewer have examined the activation pattern of these cells simultaneously.…”

Section: Introductionmentioning

confidence: 99%

Soluble markers of neutrophil, T-cell and monocyte activation are associated with disease severity and parasitemia in falciparum malaria

et al. 2018

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BackgroundThe immune response during P. falciparum infection is a two-edged sword, involving dysregulation of the inflammatory responses with several types of immune cells participating. Here we examined T-cell, monocyte/macrophage and neutrophil activation during P. falciparum infection by using soluble activation markers for these leukocyte subsets.MethodsIn a prospective cross-sectional study clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) co-infection with HIV-1, as well as HIV-infected patients with similar symptoms but without malaria (n = 58) and healthy controls (n = 52). Soluble (s)CD25, sCD14, sCD163 and myeloperoxidase (MPO) as markers for T-cell, monocyte/macrophage and neutrophil activation, respectively as well as CX3CL1, granzyme B and TIM-3 as markers of T-cell subsets and T-cell exhaustion, were analyzed.ResultsAll patient groups had raised levels of activation markers compared with healthy controls. Levels of sCD25 and MPO increased gradually from patient with HIV only to patient with malaria only, with the highest levels in the HIV/malaria group. In the malaria group as a whole, MPO, sCD14 and in particular sCD25 were correlated with disease severity. sCD163, sCD25 and in particular MPO correlated with the degree of parasitemia as assessed by qPCR. Patients with falciparum malaria also had signs of T-cell subset activation (i.e. increased granzyme B and CX3CL1) and T-cell exhaustion as assessed by high levels of TIM-3 particularly in patients co-infected with HIV.ConclusionOur data support a marked immune activation in falciparum malaria involving all major leukocyte subsets with particular enhanced activation of neutrophils and T-cells in patients co-infected with HIV. Our findings also support a link between immune activation and immune exhaustion during falciparum malaria, particularly in relation to T-cell responses in patients co-infected with HIV.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3593-8) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Soluble markers of neutrophil, T-cell and monocyte activation are associated with disease severity and parasitemia in falciparum malaria

et al. 2018

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“…Although eliminating the parasite possibly by antibodymediated processes is vital for protection, mechanisms that allow parasite tolerance without manifesting clinical symptoms, as observed in asymptomatic carriers (children and adults alike), [34][35][36] may provide clues as to how clinical immunity (antidisease immunity) to malaria is induced. These processes have, however, attracted little attention in the malaria research community.…”

Section: Introductionmentioning

confidence: 99%

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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“…It was also hypothesized that relative immunodeficiency might be enhanced when young children's circulation was inundated by malaria parasites and malaria‐related red cell antigens, hence two patient groups with and without acute malaria. A strong pro‐inflammatory response was described in acute paediatric malaria with high levels of IP10, IFN gamma, IL6 and TNF not unlike what has been observed in severe trauma . Such high level of immune disturbance might provide a situation favouring TA‐Mc.…”

Section: Discussionmentioning

confidence: 94%

“…In addition, the ‘genomic storm’ induced by massive trauma induced increased expression of genes involved in innate immune response and systemic inflammatory response . Similar responses were seen in burns and endotoxaemia but also in acute malaria . Since the blood collected by TMU is approximately 80% from male donors and the patient population 50% females, the presence of male cell marker (Y chromosome) 6 months or more post‐transfusion was detected by a sensitive genomic amplification test [quantitative real‐time PCR (qPCR)] in young female whole blood recipients.…”

Section: Methodsmentioning

confidence: 99%

Microchimerism in Ghanaian children recipients of whole blood transfusion for severe anaemia

et al. 2018

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Background and objectives Transfusion‐acquired microchimerism (TA‐Mc) has been reported in major trauma but not in young children despite relative immunodeficiency who, in sub‐Saharan Africa, often suffer severe anaemia related to haemoglobinopathies or primary malaria infections. We examined the hypothesis that such massive red cell destructions might provide conditions favourable to TA‐Mc, particularly when exposed to massive amounts of parasite antigens. Materials and Methods Twenty‐seven female children <5 years transfused with male whole blood for severe anaemia (13 with acute malaria and 14 with other causes) were retrospectively identified, and a blood sample was collected >6 months post‐transfusion. Four whole blood samples from paediatric females transfused with blood from female donors and five secondary school female students never pregnant, never transfused were used as negative controls. Results Nineteen patients (70%) carried male Mc with four (15%) having high levels of Mc (>100 genome equivalent of male cells/million of host cells) compared to three controls (37·5%). There was no difference in frequency or quantity of male Mc between paediatric patients with severe malaria and paediatric patients with other causes of severe anaemia. TA‐Mc was not correlated with patient age, duration of whole blood storage or lymphocyte load transfused. After a median of 7 months post‐transfusion, acute malaria did not increase the frequency of TA‐Mc. One negative control appeared to carry low‐level male cells. Conclusion Transfusion‐acquired microchimerism appears frequent in young children transfused with whole blood for severe anaemia.

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Monocyte dysregulation and systemic inflammation during pediatric falciparum malaria

Cited by 58 publications

References 80 publications

Soluble markers of neutrophil, T-cell and monocyte activation are associated with disease severity and parasitemia in falciparum malaria

Soluble markers of neutrophil, T-cell and monocyte activation are associated with disease severity and parasitemia in falciparum malaria

Evaluating antidisease immunity to malaria and implications for vaccine design

Microchimerism in Ghanaian children recipients of whole blood transfusion for severe anaemia

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