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  • 1. Amodu, O. K.
    et al.
    Olaniyan, S. A.
    Adeyemo, A. A.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Olumese, P. E.
    Omotade, O. O.
    Association of the sickle cell trait and the ABO blood group with clinical severity of malaria in southwest Nigeria2012In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 123, no 2, p. 72-77Article in journal (Refereed)
    Abstract [en]

    In regions of high Plasmodium falciparum malaria endemicity, certain erythrocyte polymorphisms confer resistance to severe disease. In this study, we evaluate the role of the sickle cell trait (HbS) and ABO blood groups in the clinical manifestations of childhood malaria in Southwest Nigeria. The subjects comprised 3100 children (53% males, median age 39 months), including 1400 children with uncomplicated malaria, 1000 children with asymptomatic malaria and 700 with severe malaria. Haemoglobin (Hb) types were determined using electrophoresis and serum agglutination techniques were used to determine ABO blood groups. Blood group O was the commonest ABO blood group (47.7%) in the study population, the others were A (22.5%), B (25.2%) and AB (4.6%). The frequencies of the HbAS and HbAC were 14.4% and 5.8%, respectively. In regression models adjusting for age, gender, parasite density and blood group, HbAS was associated with a reduced risk of severe malaria OR=0.46 (CI95%: 0.273-0.773). Among severe malaria subjects, HbAS was associated with significantly lower parasite densities. The protective effect of blood group 0 was demonstrated with a decreased risk of severe malaria OR=0.743 (CI95%: 0.566-0.976) after adjusting for age, gender and parasite density and Hb genotype. Blood group B was associated with increased risk of severe malaria OR=1.638 (CI95%: 1.128-2.380) after adjusting for age, gender, packed cell volume, parasite density and Hb genotype. We have confirmed from this large study of Nigerian children the major protective effective of the sickle cell heterozygous state against both cerebral malaria and severe malarial anaemia. We also show that the B blood group is associated with an increased risk of severe malaria. In conclusion, the sickle cell haemoglobin type and ABO groups modulate the risk of severe malaria in Nigerian children.

  • 2. Arama, Charles
    et al.
    Maiga, Bakary
    Dolo, Amagana
    Kouriba, Bourema
    Traore, Boubacar
    Crompton, Peter D.
    Pierce, Susan K.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Miller, Louis H.
    Doumbo, Ogobara K.
    Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?2015In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 146, p. 152-156Article, review/survey (Refereed)
    Abstract [en]

    There are many fundamental aspects of the immunobiology of Plasmodium falciparum infections that are not fully understood, therefore limiting our comprehension of how people become immune to malaria and why some ethnic groups living in malaria endemic areas are less susceptible than others. The complexity of parasite-host interactions and the genetic diversity of the parasites as well as the human host complicate our strategy to address this issue. In this mini-review we discuss and summarize what we have learned about African ethnic differences in susceptibility to malaria from immuno-epidemiological studies. Additionally, we suggest research topics that might be of great value for dissecting the mechanisms of protection by providing new insights into molecular interactions between the parasite and the host.

  • 3. Arrighi, Romanico B. G.
    et al.
    Faye, Ingrid
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Plasmodium falciparum GPI toxin: A common foe for man and mosquito2010In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 114, no 3, p. 162-165Article in journal (Refereed)
    Abstract [en]

    The glycosylphosphatidylinositol (GPI) anchor of the malaria parasite, Plasmodium falciparum, which can be regarded as an endotoxin, plays a role in the induced pathology associated with severe malaria in humans. However, it is unclear whether the main mosquito vector, Anopheles gambiae, can specifically recognize, and respond to GPI from the malaria parasite. Recent data suggests that the malaria vector does mount a specific response against malaria GPI. In addition, following the strong immune response, mosquito fecundity is severely affected, resulting in a significant reduction in viable eggs produced. In this mini-review we look at the increased interest in understanding the way that malaria antigens are recognized in the mosquito, and how this relates to a better understanding of the interactions between the malaria parasite and both human and vector.

  • 4.
    Awah, Nancy W.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Gysin, Jürg
    Unité de Parasitologie Expérimentale, URA Institut Pasteur/Univ-Med.
    Mechanisms of malarial anaemia: potential involvement of the Plasmodium falciparum low molecular weight rhoptry-associated proteins.2009In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 112, no 3, p. 295-302Article in journal (Refereed)
    Abstract [en]

    Plasmodium falciparum malaria is a major cause of morbidity and mortality throughout the tropics. Anaemia is a constant feature of the disease. Pregnant women mostly primigravidae and children below the age of 5 years are the most afflicted. Its pathogenesis is multifactorial and incompletely understood. Among several factors, the destruction of erythrocytes (RBCs) is the most frequently observed cause of severe malarial anaemia and the removal of non-parasitized RBCs (nEs) is thought to be the most important, accounting for approximately 90% of the reduction in haematocrit in acute malaria. Previous studies demonstrated that the tagging of nEs with the parasite antigen RAP-2 (rhoptry-associated protein-2; also designated RSP-2) due to either failed or aborted invasion by merozoites resulted in the destruction of these cells. In this study we further investigated the mechanisms mediating the destruction of nEs in the development of severe malarial anaemia and the possible involvement of RAP-2/RSP-2 and other members of the low molecular weight rhoptry complex (RAP-1: rhoptry-associated protein-1 and RAP-3: rhoptry-associated protein-3). Antibodies to the rhoptry-associated proteins were found to recognise the surface of nEs in a parasitaemia-dependent manner after merozoite release in P. falciparumin vitro cultures. These cells, as well as erythroblasts co-cultured with infected RBCs (IEs), could then be destroyed by either phagocytosis or lysis after complement activation. The ability of anti-rhoptry antibodies to mediate the destruction of RAP-2/RSP-2-tagged erythroblasts in the presence of effector cells was also investigated. Data obtained suggest that mouse monoclonal antibodies to the low molecular weight RAP proteins mediate the death of RAP-2/RSP-2-tagged erythroblasts on interaction with adherent monocytes. The mechanism of cell death is not yet fully known, but seems to involve primarily apoptosis. The above observations suggest that the antibody response against RAP-2/RSP-2 and other members of the complex could trigger the destruction of RAP-2/RSP-2-tagged host cells. Taken together it appears that during severe anaemia a defective bone marrow or dyserythropoiesis possibly due to erythroblast cell death, may overlap with the accelerated destruction of normal erythroid cells, either by opsonisation or complement activation further aggravating the anaemia which may become fatal. These observations could therefore have implications in the design, development and deployment of future therapeutic interventions against malaria.

  • 5.
    Balogun, Halima A.
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Awah, Nancy
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nilsson, Sandra
    Rogier, Christophe
    Trape, Jean-Francois
    Chen, Qijun
    Roussilhon, Christian
    Berzins, Klavs
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Pattern of antibodies to the Duffy binding like domain of Plasmodium falciparum antigen Pf332 in Senegalese individuals2014In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 130, p. 80-87Article in journal (Refereed)
    Abstract [en]

    Acquisition of antibodies against blood stage antigens is crucial in malaria immunity and the Plasmodium falciparum antigen Pf332, which is present in close association with the infected red blood cell membrane, is one such antigen. In this study, the antibody response to a Duffy binding like fragment of Pf332, termed Pf332-DBL was investigated in sera from naturally exposed individuals living in Dielmo village, Senegal, with regard to immunoglobulin classes (IgG, IgM, IgE) and IgG subclasses (IgG1-4). While the levels of IgM, IgG, IgG1 and IgG2 only displayed a moderate trend to increase with age, Pf332-DBL specific IgG3 levels increased significantly in the older villagers. In multivariate analysis, when controlling for confounding factors, and in a linear model with a Poisson distribution, anti-Pf332-DBL IgG3 as well as the ratio of cytophilic to non cytophilic anti-Pf332-DBL antibodies were found significantly associated with a reduced risk of malaria attack. This association was also present when the IgG3:IgG1 ratio was tested. Finally, two subgroups of villagers with the same mean age, were delineated by IgG3 concentrations either lower or higher than the median value. A total of 45.2% of the individuals with low anti-Pf332-DBL-IgG3 levels but only 21.4% of the villagers in the group with high levels of such antibodies had a clinical malaria attack during a period of 3 years of continuous follow-up after the blood sampling. In conclusion, Pf332-DBL induces naturally the acquisition of antibodies, and Pf332-DBL-specific IgG3 appears to be associated with protection against malaria in this endemic setting.

  • 6.
    Bolad, A K
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Nebie, I
    Esposito, F
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    The use of impregnated curtains does not affect antibody responses against Plasmodium falciparum and complexity of infecting parasite populations in children from Burkina Faso2004In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 90, no 3, p. 237-247Article in journal (Refereed)
    Abstract [en]

    In Burkina Faso, where malaria is hyper-endemic and transmission intensity is very high, the majority of malaria-related morbidity and mortality occurs in children less than 5 years of age. A control measure such as the use of insecticide-treated curtains (ITC) significantly reduces transmission of malaria infection. Concerns remain whether reduced transmission intensity may lead to a delay in the development of immunity in younger children and even to a partial loss of already acquired immunity. In this study, the levels of P. falciparum-specific IgG subclasses, the number of infecting parasite clones determined by PCR-based genotyping of the msp2 gene and the parasite density were analysed in 154 asymptomatic children (3–6 years) living in 16 villages (8 with and 8 without ITC) in the vicinity of Ouagadougou, the capital of Burkina Faso. In addition, the parasite inhibitory effects of Ig fractions, prepared from selected children, in co-operation with normal human monocytes were studied. Blood samples from asymptomatic ITC-users showed a significant decrease in P. falciparum prevalence as well as in parasite density. However, no significant difference was observed in P. falciparum-specific antibodies or in parasite multiplicity of infection between the two groups. Furthermore, Ig fractions from children of both groups showed similar levels of inhibitory activity against autologous parasite growth both on their own and in co-operation with monocytes.

  • 7. Cherif, Mariama K.
    et al.
    Sanou, Guillaume S.
    Bougouma, Edith C.
    Diarra, Amidou
    Ouedraogo, Alphonse
    Dolo, Amagana
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Cavanagh, David R.
    Theisen, Michael
    Modiano, David
    Sirima, Sodiomon B.
    Nebie, Issa
    Is Fc gamma receptor IIA (Fc gamma RIIA) polymorphism associated with clinical malaria and Plasmodium falciparum specific antibody levels in children from Burkina Faso?2015In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 142, p. 41-46Article in journal (Refereed)
    Abstract [en]

    In the present study, the influences of Fc gamma RIIA polymorphism on susceptibility to malaria and antibody responses to Plasmodium falciparum antigens were analyzed in children. We recruited 96 healthy children between 3 and 10 years at the beginning of the high transmission season and we followed up for 5 months through the high transmission season to assess the parasitological, immunological and genetic endpoints in relation to clinical malaria status. There was a similar distribution of homozygous and heterozygous individuals carrying the Fc gamma RIIA-131R/R and Fc gamma RIIA-131R/H allele, whereas the number of Fc gamma RIIA-131H/H homozygous individuals was lower. P. falciparum infection frequency was not associated with the Fc gamma RIIa-131R/H polymorphism. Only IgG antibody responses to GLURP R0 showed a significant association between antibody levels and Fc gamma RIIA polymorphism (p = 0.02). IgG levels to MSP2a were significantly higher in children who did not experience any clinical malaria episode compared to those who experienced at least one malaria episode (p = 0.019). Cytophilic and non-cytophylic IgG subclass levels were higher in children without malaria than those who experienced at least one malaria episode. This difference was statistically significant for IgG1 to MSP3 (p = 0.003) and to MSP2a (p = 0.006); IgG3 to MSP2a (p = 0.007) and to GLURP R0 (p = 0.044); IgG2 to MSP2b (p = 0.007) and IgG4 to MSP3 (p = 0.051) and to MSP2a (p = 0.049). In this study, homozygous carriers of the Fc gamma RIIA-131R/R allele had higher malaria-specific antibody levels compare to the heterozygous carriers Fc gamma RIIA-131R/H alleles and to homozygous carriers of Fc gamma RIIA-131H/H alleles. The pre-existing antibodies responses were related to a reduced subsequent risk of clinical malaria.

  • 8.
    Kaneko, Akira
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    A community-directed strategy for sustainable malaria elimination on islands: Short-term MDA integrated with ITNs and robust surveillance2010In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 114, no 3, p. 177-183Article in journal (Refereed)
    Abstract [en]

    In the Asia Pacific sites with low and unstable transmission, elimination should be feasible with existing tools. On Aneityum island, Vanuatu both Plasmodium falciparum and Plasmodium vivax malaria were eliminated in 1991 after implementation of a combined intervention package, including mass drug administration (MDA) and insecticide-treated bed nets (ITNs), with high degree of community involvement. Subsequently, community-based surveillance and vector control measures have kept. By reviewing the experiences of the Aneityum project, I intended to examine the roles of community in malaria elimination. To be successful, the program should transfer major intervention components from the external donor-directed initiative to the community-directed approach. Scaling up of community involvement from simple participation to social participation, where communities involve in health planning functions is necessary from malaria control to malaria elimination.

  • 9. Kumsiri, Ratchanok
    et al.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Pattanapanyasat, Kovit
    Krudsood, Srivicha
    Maneerat, Yaowapa
    IgE low affinity receptor (CD23) expression, Plasmodium falciparum specific IgE and tumor necrosis factor-alpha production in Thai uncomplicated and severe falciparum malaria patients2016In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 154, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Previous studies have suggested that Plasmodium falciparum (P. falciparum) specific IgE in the form of immune complexes crosslinking the low-affinity receptor (CD23) on monocyte results in tumor necrosis factor (TNF)-alpha and nitric oxide (NO) production. However, the roles of these parameters in severity and immune protection are still unclear. This study aimed to determine the association between CD23 expression on monocytes, plasma soluble CD23 (sCD23), total IgE, malaria-specific IgE and IgG, and TNF-alpha levels in P. falciparum infected patients. We evaluated 64 uncomplicated (UC) and 25 severe patients (S), admitted at the Hospital for Tropical Diseases, Mahidol University, and 34 healthy controls (C) enrolled in 2001. Flow cytometry and enzyme linked immunosorbent assays (ELISA) demonstrated that trends of the CD23 expression, levels of sCD23 and specific IgE were higher in the S group as compared to those in the UC and C groups. Plasma levels of P. falciparum specific IgE in the UC (p = 0.011) and S groups (p = 0.025) were significantly higher than those in C group. In contrast the TNF-alpha levels tended to be higher in the UC than those in the S (p = 0343) and significantly higher than those in C (p = 0.004) groups. The specific IgG levels in UC were significantly higher than those in S and C (p < 0.001) groups. At admission, a strong significant negative correlation was found between specific IgG and sCD23 (r = -0.762, p = 0.028), and TNF-alpha and IgE-IgG complexes (r=-0.715, p = 0.002). Significant positive correlations between levels of specific IgE and TNF-alpha (r=0.575, p = 0.010); and sCD23 (r=0.597, p = 0.000) were also observed. In conclusion, our data suggest that CD23 expression and malaria-specific IgE levels may be involved in the severity of the disease while TNF-alpha and the malaria-specific IgG may correlate with protection against falciparum malaria.

  • 10.
    Lindh, J. M.
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Borg-Karlson, A. -K
    Faye, Ingrid
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Transstadial and horizontal transfer of bacteria within a colony of Anopheles gambiae (DipteraCulicidae) and oviposition response to bacteria-containing water:  2008In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 107, no 3, p. 242-250Article in journal (Refereed)
    Abstract [en]

    In a paratransgenic approach, genetically modified bacteria are utilized to kill the parasite in the vector gut. A critical component for paratransgenics against malaria is how transgenic bacteria can be introduced and then kept in a mosquito population. Here, we investigated transstadial and horizontal transfer of bacteria within an Anopheles gambiae mosquito colony with the focus on spiked breeding sites as a possible means of introducing bacteria to mosquitoes. A Pantoea stewartii strain, previously isolated from An. gambiae, marked with a green fluorescent protein (GFP), was introduced to mosquitoes in different life stages. The following life stages or older mosquitoes in the case of adults were screened for bacteria in their guts. In addition to P. stewartii other bacteria were isolated from the guts: these were identified by 16S rRNA sequence analysis and temporal temperature gradient gel electrophoresis (TTGE). Bacteria were transferred from larvae to pupae but not from pupae to adults. The mosquitoes were able to take up bacteria from the water they emerged from and transfer the same bacteria to the water they laid eggs in. Eliza-bethkingia meningoseptica was more often isolated from adult mosquitoes than P. stewartii. A bioassay was used to examine An. gambiae oviposition responses towards bacteria-containing solutions. The volatiles emitted from the solutions were sampled by headspace-solid phase microextraction (SPME) and identified by gas chromatography and mass spectrometry (GC-MS) analysis. P. stewartii but not E. meningoseptica mediated a positive oviposition response. The volatiles emitted by P stewartii include indole and 3-methyl-1 -butanol, which previously have been shown to affect An. gambiae mosquito behaviour. E. meningoseptica emitted indole but not 3-methyl-1 -butanol, when suspended in saline. Taken together, this indicates that it may be possible to create attractive breeding sites for distribution of genetically modified bacteria in the field in a paratransgenic approach against malaria. Further research is needed to determine if the bacteria are also transferred in the same way in nature.

  • 11.
    Nyakeriga, Alice M.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology. Texas Tech University, USA; Kilifi District Hospital, Kenya.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Haptoglobin phenotypes and iron status in children living in a malaria endemic area of Kenyan coast2013In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 126, no 2, p. 127-131Article in journal (Refereed)
    Abstract [en]

    Malaria infection may be affected by host genetic factors as well as nutritional status. Iron status and the phenotype of haptoglobin, a heme-binding acute phase reactant may be determinants of malaria parasitemia. A combination of cross sectional studies and longitudinal follow-up were used to describe the association between iron status, C-reactive protein, malaria infections and host genetic factors including; haptoglobin (Hp) phenotypes, in children below 9 years in a malaria endemic area in Coastal Kenya. The prevalence of 0.45 and 0.41, respectively for Hp 1-1 and Hp 2-1 phenotypes was significantly higher than 0.14 for Hp 2-2 phenotype (n = 162). Children with Hp 2-2 phenotype showed significantly higher iron storage compared to those with Hp 1-1 and Hp 2-1 phenotypes when children with malaria parasites and high C-reactive protein (>9 mg/L) were excluded from the analysis. There were no significant differences in malaria parasite densities among Hp phenotypes but children with Hp 2-2 had lower number of clinical malaria episodes (P=0.045). Taken together, this study shows that the presence of malaria may complicate the interpretation of iron status in children based on their Hp-phenotypes. Further studies will be required to address possible interactions among the various genetic factors and iron status in a malaria endemic setting.

  • 12. Olaniyan, Subulade A.
    et al.
    Amodu, Olukemi K.
    Bakare, Adekunle A.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Omotade, Olayemi O.
    Rockett, Kirk A.
    Tumour necrosis factor alpha promoter polymorphism, TNF-238 is associated with severe clinical outcome of falciparum malaria in Ibadan southwest Nigeria2016In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 161, p. 62-67Article in journal (Refereed)
    Abstract [en]

    Tumour necrosis factor (TNF) - alpha has been shown to play an important role in the pathogenesis of falciparum malaria. Two TNF promoter polymorphisms, TNF-308 and TNF-238 have been associated with differential activity and production of TNF. In order to investigate the association between TNF-308 and TNF-238 and the clinical outcome of malaria in a Nigerian population, the two TNF polymorphisms were analysed using Sequenom iPLEX Platform. A total of 782 children; 283 children with uncomplicated malaria, 255 children with severe malaria and 244 children with asymptomatic infection (controls) were studied. The distribution of TNF-308 and TNF-238 genotypes were consistent with the Hardy-Weinberg equilibrium. Distribution of both TNF polymorphisms differed significantly across all clinical groups (TNF-308: p = 0.007; TNF-238: p=0.001). Further tests for association with severe malaria using genotype models controlling for age, parasitaemia and HbAS showed a significant association of the TNF-238 polymorphism with susceptibility to severe malaria (95% CI = 1.43-6.02, OR= 2.94, p = 0.003237) The GG genotype of TNF-238 significantly increased the risk of developing cerebral malaria from asymptomatic malaria and uncomplicated malaria (95% CI = 1.99-18.17, OR= 6.02, p <0.001 and 95% CI= 1.78-8.23, OR= 3.84, p <0.001 respectively). No significant association was found between TNF-308 and malaria outcome. These results show thegenetic association of TNF-238 in the clinical outcome of malaria in Ibadan, southwest Nigeria. These findings add support to the role of TNF in the outcome of malaria infection. Further large scale studies across multiple malaria endemic populations will be required to determine the specific roles of TNF-308 and TNF-238 in the outcome of falciparum malaria infection.

  • 13.
    Simone, Olivia
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Bejarano, Maria Teresa
    Pierce, Susan K
    Antonaci, Salvatore
    Wahlgren, Mats
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Donati, Daria
    TLRs innate immunereceptors and Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) CIDR1α-driven human polyclonal B-cell activation.2011In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 119, no 2-3, p. 144-150Article in journal (Refereed)
    Abstract [en]

    Chronic malaria severely affects the immune system and causes polyclonal B-cell activation, as evidenced by the presence of hypergammaglobulinemia, elevated levels of autoantibodies, loss of B-cell memory and the frequent occurrence of Burkitt's lymphomas (BL) in children living in malaria endemic areas. Previous studies have shown that the cysteine-rich interdomain region 1α (CIDR1α) of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) of the FCR3S1.2 strain, subsequently named CIDR1α, interacts with B cells partially through the binding to the B-cell receptor (BCR). This interaction leads to an activated phenotype, increased survival, and a low degree of proliferation. CIDR1α preferentially activates the memory B-cell compartment, therefore PfEMP1 is considered to act as a polyclonal B-cell activator and its role in memory maintenance has been suggested. In this report, we extend the analysis of the PfEMP1-CIDR1α B-cell interaction and demonstrate that PfEMP1-CIDR1α increases the expression of TLR7 and TLR10 mRNA transcripts and sensitizes B cells to TLR9 signalling via the MyD88 adaptor molecule. Furthermore, despite its ability to bind to surface Igs, PfEMP1-CIDR1α-induced B-cell activation does not seem to proceed through the BCR, since it does not induce Lyn and/or phospho-tyrosine mediated signalling pathways. Rather PfEMP1-CIDR1α induces the phosphorylation of downstream kinases, such as ERK1/2, p38 and IKBα, in human B cells. These findings indicate that PfEMP1-CIDR1α induces a persistent activation of B cells, which in turn can contribute to the exhaustion and impairment of B-cell functions during chronic malaria infection.

  • 14.
    Vafa, Manijeh
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Israelsson, Elisabeth
    Maiga, Bakary
    Dolo, Amagana
    Doumbo, Ogobara K.
    Troye-Blomberg, Marita
    Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali2009In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 9, no 1, p. 12-16Article in journal (Refereed)
    Abstract [en]

    This study aimed to assess correlations between anti-malarial antibody levels and differences in malariometric characteristics, seen between two sympatric ethnic groups, the Fulani and the Dogon, living in Mali. Plasma levels of anti-malarial IgE, IgG. IgG1-4 and total IgE were determined in asymptomatic individuals, of the above mentioned groups, and were correlated to malariometric indexes. Significantly higher levels of anti-malarial IgE, IgG, IgG1-3 and total IgE were detected in the Fulani individuals as compared to the Dogon. No difference in plasma levels of malaria specific IgG4 was noted between the two groups. Within the Fulani, an increase in total IgE levels was associated with the presence of infection. As the IgG4 level increased, the number of clones decreased in the Fulani individuals. A positive correlation between elevated levels of anti-malarial IgG and IgG3 and splenomegaly was noted only within the Fulani group. No other correlations between antibody levels and parasite prevalence, clone numbers or spleen rates were observed in any of the communities. These results suggest that the magnitude of antibody response against Plasmodium falciparum may not be as important as it is believed to be. Instead, the fine specificity or function of the response might be more critical in protection against malaria disease.

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