Association of Early Interferon‐γ Production with Immunity to Clinical Malaria: A Longitudinal Study among Papua New Guinean Children

D’Ombrain, Marthe C.; Robinson, Leanne J.; Stanisic, Danielle I.; Taraika, J.; Bernard, Nicholas J.; Michon, P; Müeller, Ivo; Schofield, Louis

doi:10.1086/592971

Cited by 140 publications

(149 citation statements)

References 37 publications

Supporting

Mentioning

141

Contrasting

Order By: Relevance

“…The finding presented herein agrees with earlier studies that malaria induces immune stimulation (Inigo and Manuel, 2002;Sacks et al, 2003), resulting in increased secretion of cytokines. Phagocytosis of the parasite or the haemozoin, glycosilphosphatidylinositol (GPI) and the parasite toxin also causes immune stimulation evinced by up-regulation of cytokines (Venugopal, 2007;D'Ombrain et al, 2008). Moreover, reactive oxygen species such as hydrogen peroxide (H2O2), hydroxyl (OH -) and superoxide (O2 -) generated during oxidative stress activates leucocytes with the release of more cytokines (Kumar et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

Peripheral Parasitaemia and Its Association With Plasma Cytokines Levels in Malaria-Infected Pregnant Women in Aba, Abia State, Nigeria

Ifeanyichukwu

Okamgba

Amilo

et al. 2017

AJID

View full text Add to dashboard Cite

Background: Cytokines in pregnant female may not be a normal phenomenon as malarial infection is often associated with strong CD4+ cell activation and up-regulation of pro-inflammatory cytokines. We investigated the relationship between peripheral parasitaemia and plasma levels of cytokines among malaria infected pregnant women in Aba, Abia State, Nigeria. Materials and Methods: A total of 206 non-HIV positive asymptomatic malaria parasitaemic (n=144) and non-parasitaemic (n=62) pregnant women were recruited for this study alongside 80 non-pregnant women who served as positive (n=40) and negative (n=40) controls. Blood samples were aseptically collected from each subject and tested for HIV and malaria parasites using standard methods. Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student's t-test were used for Comparison of groups while Pearson's Correlation Coefficient was used for tests of association. Results:The results revealed a mean parasite density of 685.56±484.55 parasites/µl of blood. Malaria infected pregnant subjects showed significantly higher levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-10 when compared with their non-infected counterparts (P< 0.05). The cytokines evaluated were higher in moderate parasitaemia than mild parasitaemia. Positive correlation existed between peripheral parasite density (PPD) and IL-4 (r= 0.24, P=0.004), PPD and IL-6 (r = 0.35, P = 0.001) as well as PPD and IL-10 (r = 0.29, P = 0.001). Conclusion:This study showed that increase in peripheral parasitaemia increased levels of some plasma cytokines (IL-4, IL-6 and IL-10) but not IFN-γ and TNF-α in the malaria infected pregnant women studied.

show abstract

Section: Resultsmentioning

confidence: 99%

Peripheral Parasitaemia and Its Association With Plasma Cytokines Levels in Malaria-Infected Pregnant Women in Aba, Abia State, Nigeria

Ifeanyichukwu

Okamgba

Amilo

et al. 2017

AJID

View full text Add to dashboard Cite

show abstract

“…On average, NK cells comprised 8.0% of the total cells, ␥␦-T cells comprised 5.8% of the total cells, ␣␤-T cells comprised 64.9% of the total cells, and 21.4% of the cells were other cells. ␥␦-T cells and ␣␤-T cells were previously identified by flow cytometric intracellular IFN-␥ staining as the predominant source of P. falciparum-induced IFN-␥ in the malariaexposed children examined, with a minor contribution by NK cells (10). Similar to IFN-␥ production, several cell types are capable of producing IL-6 and TNF, and the role of these cytokines during malaria infection may vary depending on their cellular origin.…”

Section: Figmentioning

confidence: 96%

“…For malaria-exposed individuals, Dodoo et al (8) reported an association between late-stage, live P. falciparuminduced IFN-␥ production and reduced risk of fever and clinical malaria. More recently, we reported that early P. falciparum-induced IFN-␥ production from ␥␦-T cells and ␣␤-T cells is associated with protection from clinical P. falciparum episodes in a cohort of 5-to 14-year-old children from a region of Papua New Guinea (PNG) where malaria is endemic (10).…”

mentioning

confidence: 99%

Cellular Tumor Necrosis Factor, Gamma Interferon, and Interleukin-6 Responses as Correlates of Immunity and Risk of Clinical Plasmodium falciparum Malaria in Children from Papua New Guinea

et al. 2009

Self Cite

View full text Add to dashboard Cite

The role of early to intermediate Plasmodium falciparum-induced cellular responses in the development of clinical immunity to malaria is not well understood, and such responses have been proposed to contribute to both immunity and risk of clinical malaria episodes. To investigate whether P. falciparum-induced cellular responses are able to function as predictive correlates of parasitological and clinical outcomes, we conducted a prospective cohort study of children (5 to 14 years of age) residing in a region of Papua New Guinea where malaria is endemic Live, intact P. falciparum-infected red blood cells were applied to isolated peripheral blood mononuclear cells obtained at baseline. Cellular cytokine production, including production of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF) (formerly tumor necrosis factor alpha), and gamma interferon (IFN-␥), was measured, and the cellular source of key cytokines was investigated. Multicytokine models revealed that increasing P. falciparum-induced IL-6 production was associated with an increased incidence of P. falciparum clinical episodes (incidence rate ratio [ Individuals living in regions of moderate to high malaria endemicity slowly acquire clinical immunity to Plasmodium falciparum throughout their lives in an age-and exposuredependent manner (3,29). This immunity enables them to control parasite replication at densities below that which induces clinical symptoms (29,46). Both antibody-dependent and T-cell-dependent acquired immune responses have been shown to play an important role in the development of clinical immunity (13,29). The role of early to intermediate cellular responses, however, is less well understood, and such responses have been proposed to contribute to both immunity and risk of clinical malaria episodes (45,49,51).Early cellular immune responses are rapidly initiated during malaria infection and are thought to play an important role both in limiting initial parasite replication and in directly shaping subsequent adaptive immune responses (45,49,51). However, the overproduction or inappropriate regulation of both proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, gamma interferon (IFN-␥), and tumor necrosis factor (TNF) (formerly tumor necrosis factor alpha), and anti-inflammatory cytokines, such as IL-10, IL-4, and transforming growth factor ␤ (TGF-␤), may also lead to localized and systemic inflammation and has been associated with symptomatic and severe malaria (7,45). The clinical outcome of an infection may thus depend on the appropriate induction and counterregulation of both pro-and anti-inflammatory cytokine secretion. Understanding how this network of P. falciparum-induced cellular responses is associated with immunity and risk of clinical disease in malaria exposed-children could provide important insights for the development of effective vaccines.Studies investigating the association between P. falciparumor antigen-induced secretion of cytokines from peripheral blood mononuclear cells (PBMCs) and prosp...

show abstract

“…Fifty-five percent of volunteers at baseline had measurable IFN-␥ ELISPOT responses, and while there was an increase in IFN-␥ production after three vaccinations, there was no statistical difference in outcomes between volunteers who received the AMA1 candidate vaccine and those who received the rabies control vaccine. This phasecreased cellular immunity and/or induction of antibody-dependent cell-mediated inhibition (ADCI) (12). Alternatively, the MSP1 33 variant may, through T-cell help, be the determinant of effective MSP1 19 humoral responses.…”

Section: Downloaded Frommentioning

confidence: 99%

Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

et al. 2010

View full text Add to dashboard Cite

Cross-sectional seroepidemiological studies of populations naturally exposed to Plasmodium falciparum suggest an association between protection from malaria and circulating antibodies to the carboxyl terminus of merozoite surface protein 1 (MSP1) Infection with Plasmodium spp., the protozoan parasites responsible for malaria, results in an estimated 350 to 500 million infections per year with an ensuing 1 to 2 million deaths, the majority of which are caused by Plasmodium falciparum (45). Adults who have maintained lifelong residence in areas where malaria transmission is stable and of high intensity gradually develop naturally acquired immunity, an age-related phenomenon marked by a reduced frequency and severity of clinical malaria and high-density blood stage parasitemia relative to that of infants and children. Maintaining naturally acquired immunity is thought to require continuing exposure to malaria blood stage antigens mediated through asymptomatic low-density blood stage infection. A malaria vaccine that would accelerate the development of naturally acquired immunity during infancy and childhood has been a high priority for many years. The recent success of vector interventions, such as insecticidetreated bed nets, in decreasing transmission of P. falciparum in sub-Saharan Africa suggests that a blood stage vaccine would also be desirable in order to maintain the strength and duration of naturally acquired immunity among adults (17)..Merozoite surface protein 1 (MSP1) is one of several candidates that have been considered for a blood stage vaccine. The primary ϳ195-kDa MSP1 protein is expressed during schizogony and is processed initially to form a 42-kDa carboxyl-terminal fragment (MSP1 42 ) that remains attached to the merozoite surface. A second proteolytic cleavage results in the shedding of a 33-kDa fragment (MSP1 33 ) with formation of a 19-kDa carboxyl-terminal fragment (MSP1 19 ) anchored to the merozoite surface during invasion of the red blood cell (RBC) (4, 5). The 19-kDa fragment of MSP1 contains the major B-cell epitopes (18), the recognition of which is enhanced by T-helper epitopes in the 33-kDa fragment (1). Antibodies to MSP1 19

show abstract

Association of Early Interferon‐γ Production with Immunity to Clinical Malaria: A Longitudinal Study among Papua New Guinean Children

Abstract: High, early IFN-gamma production by live parasite-stimulated peripheral blood mononuclear cells is a correlate of immunity to symptomatic malaria in Papua New Guinean children, and natural killer-like gammadelta T cells may contribute to protection.

Cited by 140 publications

References 37 publications

Peripheral Parasitaemia and Its Association With Plasma Cytokines Levels in Malaria-Infected Pregnant Women in Aba, Abia State, Nigeria

Peripheral Parasitaemia and Its Association With Plasma Cytokines Levels in Malaria-Infected Pregnant Women in Aba, Abia State, Nigeria

Cellular Tumor Necrosis Factor, Gamma Interferon, and Interleukin-6 Responses as Correlates of Immunity and Risk of Clinical Plasmodium falciparum Malaria in Children from Papua New Guinea

Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

Contact Info

Product

Resources

About