ORCID Profile
0000-0002-5851-3373
Current Organisation
World Health Organization
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Publisher: Cambridge University Press (CUP)
Date: 07-01-2016
DOI: 10.1017/S0031182015001249
Abstract: With increasing malaria control and goals of malaria elimination, many endemic areas are transitioning from high-to-low-to-no malaria transmission. Reductions in transmission will impact on the development of naturally acquired immunity to malaria, which develops after repeated exposure to Plasmodium spp. However, it is currently unclear how declining transmission and malaria exposure will affect the development and maintenance of naturally acquired immunity. Here we review the key processes which underpin this knowledge the amount of Plasmodium spp. exposure required to generate effective immune responses, the longevity of antibody responses and the ability to mount an effective response upon re-exposure through memory responses. Lastly we identify research priorities which will increase our understanding of how changing transmission will impact on malarial immunity.
Publisher: Springer Science and Business Media LLC
Date: 03-01-2017
Publisher: Public Library of Science (PLoS)
Date: 24-06-2011
Publisher: Springer Science and Business Media LLC
Date: 2005
Publisher: Elsevier BV
Date: 09-2007
DOI: 10.1016/J.MICINF.2007.05.019
Abstract: T cells are thought to play a critical role in cerebral malaria pathogenesis. However, available evidences are restricted to rodent models in which V beta specific T cell expansion has been associated with neurological syndrome suggesting involvement of superantigens or dominant antigens. Using flow cytometry, we studied the peripheral V beta T cell repertoire of Ghanaian children with cerebral malaria, uncomplicated malaria and asymptomatic control children, to look for either expansion or deletion of specific V beta associated with cerebral malaria. At admission, the general pattern of the repertoire of the patients was very similar, with no major distortion compared to the control group a part a significant increase of the frequency of the V beta 21.3 subset correlating with disease severity and attributed to the CD4 subset. During convalescence very limited fluctuations were observed including a significant decrease of the V beta 21.3 subset and increase of the V beta 20 subset, a subset not detected at admission. The remarkable stability of the V beta repertoire observed in acute malaria either cerebral or uncomplicated argues against the idea that cerebral malaria would result from a T cell-mediated inflammatory shock syndrome driven by some dominant super-antigenic activity(ies). The significance of the reproducible increase of the CD4+V beta 21.3T cell subset deserves further investigations.
Publisher: Frontiers Media SA
Date: 29-01-2016
Publisher: Public Library of Science (PLoS)
Date: 10-11-2017
Publisher: Oxford University Press (OUP)
Date: 15-11-2006
DOI: 10.1086/508547
Abstract: Respiratory distress (RD), a symptom of underlying metabolic acidosis, has been identified as a major risk factor for mortality in children with severe malaria in Africa, yet the molecular mediators involved in the pathogenesis of RD have not been identified. We studied circulating levels of mediators of inflammation--including the cytokines tumor necrosis factor (TNF)- alpha and interleukin (IL)-10 the chemokines macrophage inflammatory protein (MIP)-1 alpha , MIP-1 beta , and IL-8 and the immune activation marker neopterin--in children with RD, severe malarial anemia (SMA), cerebral malaria (CM), and uncomplicated malaria (UM). Children with RD had significantly higher plasma levels of TNF- alpha , IL-10, and neopterin and a significantly higher TNF- alpha : IL-10 ratio than those without RD. In addition, the results demonstrated that, relative to UM, CM was associated with increased levels of TNF- alpha and decreased levels of MIP-1 alpha , whereas SMA was associated with decreased levels of IL-10. Circulating levels of neopterin were inversely correlated with hemoglobin, whereas levels of MIP-1 beta were positively correlated with parasitemia. We conclude that distinct clinical presentations of severe malaria are associated with specific patterns of inflammatory mediators. In particular, we show, to our knowledge for the first time, that patients with malaria and RD have a strong and unbalanced proinflammatory response that may be involved in the pathogenesis of the underlying metabolic acidosis.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 03-2021
Publisher: No publisher found
Date: 2014
Publisher: Springer Science and Business Media LLC
Date: 19-03-2021
DOI: 10.1038/S41467-021-21998-4
Abstract: A highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high efficacy. Here, we identify key roles in humoral immunity for Fcγ-receptor (FcγR) interactions and opsonic phagocytosis of sporozoites. We identify a major role for neutrophils in mediating phagocytic clearance of sporozoites in peripheral blood, whereas monocytes contribute a minor role. Antibodies also promote natural killer cell activity. Mechanistically, antibody interactions with FcγRIII appear essential, with FcγRIIa also required for maximum activity. All regions of the circumsporozoite protein are targets of functional antibodies against sporozoites, and N-terminal antibodies have more activity in some assays. Functional antibodies are slowly acquired following natural exposure to malaria, being present among some exposed adults, but uncommon among children. Our findings reveal targets and mechanisms of immunity that could be exploited in vaccine design to maximize efficacy.
Publisher: Springer New York
Date: 2015
DOI: 10.1007/978-1-4939-2815-6_12
Abstract: Infection with Plasmodium falciparum parasites causes the majority of malaria-related morbidity and mortality. Constant exposure to the pathogen leads to the acquisition of antibodies and high levels of antibodies have been associated with clinical protection against malaria. A possible protective mechanism is the opsonization of parasites, or malaria-infected erythrocytes (IEs), for phagocytic clearance. Current assays use adherent or chemically differentiated THP-1 cells to evaluate opsonic antibodies in patients' s les, but these assays are often time consuming and damage the effector cells. We have developed a high throughput flow cytometry-based phagocytosis assay using undifferentiated THP-1 cells to quantify the opsonic activity against late stage P. falciparum-IEs. Opsonic antibodies bound to IEs promote their phagocytic uptake through Fcγ receptors found on THP-1 cells. Moreover, undifferentiated THP-1 cells do not express CD36, a surface scavenger receptor that promotes non-opsonic phagocytosis. This technical advance allows quantification of opsonic antibodies and is an important tool for the performance of large, population-based studies of malaria immunity, and to provide a significant increase in the statistical power for such studies.
Publisher: Public Library of Science (PLoS)
Date: 07-02-2013
Publisher: Springer Science and Business Media LLC
Date: 08-2012
Abstract: Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo , but little is known about the activation status of those cells in SMA patients. The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in s les collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR + and/or CD69 + surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined. Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69 + and HLA-DR + T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM ( P = .003) and UM ( P = .004). Although in SMA the IL-10 response to LPS-stimulation was larger in litude than in CM ( P = .0082), the absolute levels of IL-10 reached were lower ( P = .013). Both the litude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM ( P = .019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM ( P = .005) contrasting with TNF levels, which were higher ( P = .001). These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming olarization pattern in response to infection.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.IJPARA.2014.12.002
Abstract: During gestational malaria, Plasmodium falciparum-infected erythrocytes can sequester within the placenta, contributing to poor pregnancy outcomes, especially low birth weight. In children and non-pregnant adults, pigmented leukocytes may serve as markers of sequestered parasite burden and predict clinical outcomes. Here, we investigated circulating pigmented leukocyte numbers as predictors of clinical outcomes in pregnant women presenting with malaria at enrolment. The number of circulating pigmented neutrophils at enrolment negatively correlated with birth weight (Rho=-25, P=.04), suggesting these cells may have a pathogenic role in, and could serve as prognostic markers for, malaria-associated low birth weight.
Publisher: Elsevier BV
Date: 03-2013
Publisher: Oxford University Press (OUP)
Date: 10-12-2014
Abstract: Placental malaria, especially when complicated with intervillositis, can cause fetal growth restriction. Transplacental glucose transport by glucose transporter isoform 1 (GLUT-1) on the syncytiotrophoblast microvillous and basal plasma membranes regulates fetal growth. We found that GLUT-1 expression in the microvillous plasma membrane of Plasmodium falciparum-negative placenta biopsy specimens was comparable to that in P. falciparum-positive placenta biopsy specimens with or without intervillositis, whereas GLUT-1 expression in the basal plasma membrane was lowest in P. falciparum-positive placenta biopsy specimens with intervillositis, compared with the other 2 specimen types (P ≤ .0016). GLUT-1 expression in the basal plasma membrane also correlated negatively with monocyte infiltrate density (r = -0.43 P = .003) and positively with birth weight (r = 0.28 P = .06). These findings suggest that intervillositis, more than placental malaria per se, might cause fetal growth restriction, through impaired transplacental glucose transport.
Publisher: Public Library of Science (PLoS)
Date: 22-05-2013
Publisher: The Company of Biologists
Date: 2013
DOI: 10.1242/JCS.124719
Abstract: The spectrum of tumors due to overexpression of c-Myc and the loss of BLM are very similar. Hence it was hypothesized that the presence of BLM may negatively regulate c-Myc functions. Using multiple isogenic cellines it was observed that the decreased endogenous c-Myc levels in presence of BLM were reversed by treatment with proteasomal inhibitors, thereby indicating that BLM enhanced c-Myc turnover. While the N-terminal region of BLM interacted with c-Myc, the rest of the helicase contacted with c-Myc's E3 ligase, Fbw7. The two BLM domains acted as “cl /adaptor”, enhancing the binding of c-Myc to Fbw7. BLM promoted Fbw7-dependent K48-linked c-Myc ubiquitylation and its subsequent degradation in a helicase independent manner. A subset of BLM-regulated genes that were also c-Myc targets were determined and validated at both RNA and protein levels. To obtain in vivo validation of the effect of BLM on c-Myc mediated tumor initiation, isogenic cells from colon cancer cells either expressing or not expressing BLM were manipulated to inducibly shut down the expression of c-Myc. Using these cell lines the metastatic potential and the rate of initiation of tumors in nude mice were determined. The presence of BLM decreased c-Myc mediated invasiveness and delayed tumor initiation in mouse xenograft model. Consequently in tumors expressing BLM but not c-Myc, decreased ratio of proliferation over apoptosis was observed coupled with suppressed expression of angiogenesis marker, CD31. Hence BLM acts as a “caretaker tumor suppressor” due to its regulation of c-Myc stability.
Publisher: Cold Spring Harbor Laboratory
Date: 23-05-2020
DOI: 10.1101/2020.05.22.109983
Abstract: There is a pressing need for detailed knowledge of the range of pathogens, extent of co-infection and clinical impact of reproductive tract infections (RTIs) among pregnant women. Here, we report on RTIs ( Mycoplasma genitalium, Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , Treponema pallidum subspecies pallidum, bacterial vaginosis and vulvovaginal candidiasis) and other sexual and reproductive health indicators among 699 pregnant women in Papua New Guinea (PNG). We found widespread M. genitalium infection (12.5% of women), the first time this pathogen has been reported in PNG, with no evidence of macrolide resistance. Most pregnant women (76.2%) had at least one RTI, most of which are treatable. Excluding syphilis, sexually-transmitted infections were detected in 37.8% women. Syndromic management of infections is greatly inadequate and there was remarkably little use of contraception 98.4% report never having used barrier contraception. This work has implications for improving maternal and child health in PNG. This first report of Mycoplasma genitalium in Papua New Guinea finds a high burden (12.5%) among 699 pregnant women. Additionally, more than one in two women were positive for a treatable reproductive tract infection associated with poor health outcomes.
Publisher: Elsevier BV
Date: 2013
Abstract: Recruitment and activation of monocytes and macrophages are essential for clearance of malaria infection, but these have also been associated with adverse clinical outcomes. In this review we discuss recent discoveries on how distinct molecular interactions between monocytes, macrophages, and malaria parasites may alter the balance between protection and pathology in malaria-infected in iduals. The immunopathology of severe malaria often originates from excessive immune activation by parasites. The involvement of monocytes and macrophages in these events is highlighted, and priorities for future research to clarify the roles of these cells in malaria are proposed. Knowledge of the factors influencing the balance between protection and pathology can assist in the design of therapeutics aimed at modulating monocyte and macrophage functions to improve outcomes.
Publisher: Cambridge University Press (CUP)
Date: 25-10-2007
DOI: 10.1017/S003118200700011X
Abstract: Malaria infection during pregnancy is associated with poor maternal and foetal outcomes including low birth weight. In malaria-endemic areas, low birth weight is primarily a consequence of foetal growth restriction. Little is known on the pathogenesis of foetal growth restriction and our understanding of the relationship between epidemiological observations and the pathogenesis or consequences of disease is incomplete. In this review, we describe these gaps in our knowledge and also try to identify goals for future research into malaria in pregnancy. Foetal growth restriction results from a complex four-dimensional interaction between the foetus, the mother and the malaria parasite over gestation, and research into its pathogenesis may be advanced by combining longitudinal studies with techniques and approaches new to the field of malaria in pregnancy. Such approaches would greatly increase our knowledge on the pathogenesis of this disease and may provide new avenues for intervention strategies.
Publisher: Springer Science and Business Media LLC
Date: 09-05-2015
Publisher: Oxford University Press (OUP)
Date: 03-2008
DOI: 10.1086/526521
Publisher: Oxford University Press (OUP)
Date: 07-01-2011
Location: France
No related grants have been discovered for Philippe Boeuf.