1.
Nilsson, C, et al.
(författare)
Epstein-Barr virus and cytomegalovirus are differentially associated with numbers of cytokine-producing cells and early atopy
2009
Ingår i: Clinical and Experimental Allergy. - Oxford : Blackwell. - 0954-7894 .- 1365-2222. ; 39:4, s. 509-517
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND: We have previously shown that Epstein-Barr virus (EBV) seropositivity, at 2 years of age, was inversely related to IgE-sensitization and that this effect was enhanced when EBV is combined with cytomegalovirus (CMV) seropositivity. We hypothesize that early exposure to EBV or CMV will affect the cytokine balance in the individual.OBJECTIVE: The aim of this study was to relate the cytokine profile in peripheral blood mononuclear cells (PBMC) to the EBV and CMV serostatus and IgE-sensitization in children at 2 years of age.METHODS: Seventy-five children were followed prospectively from birth until 2 years of age. Their EBV and CMV serostatus was correlated to the numbers of IFN-gamma, IL-4, IL-10 and IL-12-producing PBMC following PHA stimulation in vitro. Skin prick tests and allergen-specific IgE antibodies were used to assess IgE-sensitization.RESULTS: In the study cohort, there was an inverse association between EBV seropositivity and IgE-sensitization but not with CMV seropositivity. Following linear regression analysis, we did not detect any statistically significant associations between children with IgG antibodies against EBV at 2 years of age and the investigated cytokines. However, there was a non-significant tendency to a positive association between high numbers of all individual cytokine-producing cells and EBV seropositivity. Children who were CMV seropositive had significantly higher numbers of IFN-gamma and lower numbers of IL-4-producing cells compared with CMV negative children. There was a significant, positive association between the number of IL-4-producing cells and IgE-sensitization.CONCLUSION: Taken together our results indicate that infections with EBV and CMV in different ways will interact with the immune system and may protect children from developing early atopy.
2.
Courtin, David, et al.
(författare)
G6PD A-variant influences the antibody responses to Plasmodium falciparum MSP2.
2011
Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 11:6, s. 1287-1292
Tidskriftsartikel (refereegranskat) abstract
High antibody levels directed to Plasmodium falciparum merozoite surface proteins (MSP), including MSP2, as well as genetically related red blood cell defects, have previously been found to be associated with protection against malaria. Here, our main objective was to study the changes in MSP2-specific total IgG, IgG1 and IgG3 responses during a malaria transmission season in order to assess the impact of sickle-cell, α(+)-thalassemia and G6PD variants on antibody kinetics. Repeated parasitological assessments of a cohort of children were conducted during an 8-month period. Antibody responses to recombinant MSP2/3D7 and MSP2/FC27 proteins were measured at the beginning and at the end of transmission season. We found that (i) the period of last Plasmodium falciparum infection during the transmission season was associated with IgG3 anti-MSP2 change. Compared to the IgG3 levels of children infected in January 2003 (end of transmission season), the IgG3 level of children decreased with the length of the period without infection, (ii) G6PD A- carriers had a lower increase of IgG3 levels to MSP2/FC27 and MSP2/3D7 during the transmission season than the noncarriers. This latter finding is suggestive of qualitative and/or quantitative reduction of exposure to malarial antigens related to this genetic variant, leading to weaker stimulation of specific antibody responses. We speculate that cell-mediated immune activity may explain the clinical protection afforded by this genetic trait.
3.
Giusti, Pablo, et al.
(författare)
Plasmodium falciparum-infected erythrocytes and beta-hematin induce partial maturation of human dendritic cells and increase their migratory ability in response to lymphoid chemokines.
2011
Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 79:7, s. 2727-2736
Tidskriftsartikel (refereegranskat) abstract
Acute and chronic Plasmodium falciparum infections alter the immune competence of the host possibly through changes in dendritic cell (DC) functionality. DCs are the most potent activators of T cells, and migration is integral to their function. Mature DCs express lymphoid chemokine receptors (CCRs), expression of which enables them to migrate to the lymph nodes, where they encounter naïve T cells. The present study aimed to investigate the impact of the synthetic analog to malaria parasite pigment hemozoin, i.e., β-hematin, or infected erythrocytes (iRBCs) on the activation status of human monocyte-derived DCs and on their expression of CCRs. Human monocyte-derived DCs partially matured upon incubation with β-hematin as indicated by an increased expression of CD80 and CD83. Both β-hematin and iRBCs provoked the release of proinflammatory and anti-inflammatory cytokines, such as interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha, but not IL-12, and induced upregulation of the lymphoid chemokine receptor CXCR4, which was coupled to an increased migration to lymphoid ligands. Taken together, these results suggest that the partial and transient maturation of human myeloid DCs upon stimulation with malaria parasite-derived products and the increased IL-10 but lack of IL-12 secretion may lead to suboptimal activation of T cells. This may in turn lead to impaired adaptive immune responses and therefore insufficient clearance of the parasites.
4.
Simone, Olivia, et al.
(författare)
TLRs innate immunereceptors and Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) CIDR1α-driven human polyclonal B-cell activation.
2011
Ingår i: Acta Tropica. - : Elsevier BV. - 0001-706X .- 1873-6254. ; 119:2-3, s. 144-150
Tidskriftsartikel (refereegranskat) abstract
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.
5.
Iriemenam, Nnaemeka C., et al.
(författare)
Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan
2009
Ingår i: Vaccine. - Amsterdam : Elsevier. - 0264-410X .- 1873-2518. ; 27:1, s. 62-71
Tidskriftsartikel (refereegranskat) abstract
Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.
6.
Tjärnlund, Anna, et al.
(författare)
Polymeric Ig receptor knockout mice are more susceptible to mycobacteria infection in the respiratory tract
2006
Ingår i: International Immunology. - : Oxford university press. - 0953-8178 .- 1460-2377. ; 18:5, s. 807-816
Tidskriftsartikel (refereegranskat) abstract
It is generally accepted that cellular, and not humoral immunity, plays the crucial role in defense against intracellular bacteria. However, accumulating data indicate the importance of humoral immunity for the defense against a number of intracellular bacteria, including mycobacteria. We have investigated the role of secretory IgA, the main isotype found in mucosal tissues, in protection against mycobacterial infection, using polymeric IgR (pIgR)-deficient mice. Characterization of the humoral response induced after intra-nasal immunizations with the mycobacterial antigen PstS-1 revealed a loss of antigen-specific IgA response in saliva from the knockout mice. IgA level in the bronchoalveolar lavage of knockout mice was similar to wild-type level, although the IgA antibodies must have reached the lumen by other means than pIgR-mediated transport. Infection with Mycobacterium bovis bacillus Calmette–Guérin (BCG) demonstrated that the immunized pIgR−/− mice were more susceptible to BCG infection than immunized wild-type mice, based on higher bacterial loads in the lungs. This was accompanied by a reduced production of both IFN-γ and tumor necrosis factor-alpha (TNF-α) in the lungs. Additionally, the pIgR−/− mice displayed reduced natural resistance to mycobacterial infection proved by significantly higher bacterial growth in their lungs compared with wild-type mice after infection with virulent Mycobacterium tuberculosis. The knockout mice appeared to have a delayed mycobacteria-induced immune response with reduced expression of protective mediators, such as IFN-γ, TNF-α, inducible nitric oxide synthase and regulated upon activation normal T cell sequence, during early infection. Collectively, our results show that actively secreted IgA plays a role in protection against mycobacterial infections in the respiratory tract, by blocking entrance of bacilli into the lungs, in addition to modulation of the mycobacteria-induced pro-inflammatory response.
7.
Arama, Charles, 1975-, et al.
(författare)
Interethnic Differences in Antigen-Presenting Cell Activation and TLR Responses in Malian Children during Plasmodium falciparum Malaria
2011
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:3, s. e18319-
Tidskriftsartikel (refereegranskat) abstract
The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs), and in particular dendritic cells (DCs) are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR) responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR signalling may be of importance for the protective immunity against malaria observed in the Fulani.
8.
Chuangchaiya, S, et al.
(författare)
Immune response to Plasmodium vivax has a potential to reduce malaria severity
2010
Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 160:2, s. 233-239
Tidskriftsartikel (refereegranskat) abstract
Summary Plasmodium falciparum infection causes transient immunosuppression during the parasitaemic stage. However, the immune response during simultaneous infections with both P. vivax and P. falciparum has been investigated rarely. In particular, it is not clear whether the host's immune response to malaria will be different when infected with a single or mixed malaria species. Phenotypes of T cells from mixed P. vivax-P. falciparum (PV-PF) infection were characterized by flow cytometry, and anti-malarial antibodies in the plasma were determined by an enzyme-linked immunosorbent assay. We found the percentage of CD3(+)delta2(+)-T cell receptor (TCR) T cells in the acute-mixed PV-PF infection and single P. vivax infection three times higher than in the single P. falciparum infection. This implied that P. vivax might lead to the host immune response to the production of effector T killer cells. During the parasitaemic stage, the mixed PV-PF infection had the highest number of plasma antibodies against both P. vivax and P. falciparum. Interestingly, plasma from the group of single P. vivax or P. falciparum malaria infections had both anti-P. vivax and anti-P. falciparum antibodies. In addition, antigenic cross-reactivity of P. vivax or P. falciparum resulting in antibodies against both malaria species was shown in the supernatant of lymphocyte cultures cross-stimulated with either antigen of P. vivax or P. falciparum. The role of delta2 +/- TCR T cells and the antibodies against both species during acute mixed malaria infection could have an impact on the immunity to malaria infection.
9.
Giha, Hayder A., et al.
(författare)
Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria.
2009
Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 8:1
Tidskriftsartikel (refereegranskat) abstract
ABSTRACT: BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from Daraweesh, an area of seasonal malaria transmission in Sudan, were followed for nine years for malaria infection. Total IgG and IgG isotypes against four malaria antigens, MSP2-3D7, MSP2-FC27, AMA1, and Pf332-C231 were measured in plasma obtained from the cohort at the end of the study, during the dry malaria-free period. The GM/KM allotypes of the donors were determined. RESULTS: The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly higher baseline levels of total IgG and non-cytophilic IgG isotypes as compared to non-carriers. The KM allotypes influence on IgG isotypes level was limited. Finally, the differences in the baseline concentrations of total IgG and IgG isotypes between the different GK/KM phenotype carriers were antigen-dependent. DISCUSSION: The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible CONCLUSIONS: The GM allotypes have significant influence on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses.
10.
Giusti, Pablo, 1975-
(författare)
Dendritic cells and Plasmodium falciparum: studies in vitro and in the human host
2009
Licentiatavhandling (övrigt vetenskapligt/konstnärligt) abstract
Malaria is one of the world’s most threatening diseases. About half the world’s population is at risk of infection and the infection claims a million lives each year. A vast majority of the deaths occur in children below the age of 5 in sub-Saharan Africa. Survivors typically acquire immunity only after long time of repeated exposure and immunity is rapidly lost. Immunity is created by the activation of naive T cells and their differentiation into effector cells. The most potent activators of naive T cells are dendritic cells (DCs). The life cycle of DCs is adapted to find and process microbes in order to be able to present their antigens to T cells and thereby activate them. Antigen presentation typically takes place in the lymph nodes and that is why migration to these areas is an essential part of the DC life cycle. Various studies have shown that DC function may be hampered by the malaria parasite or its components. We have investigated activation and migratory capacities of DCs upon in vitro exposure of the malarial pigment hemozoin and Plasmodium falciparum infected red blood cells. Furthermore, we have assessed the activation status of blood DCs in the Fulani, a traditionally nomadic population that respond better to malaria infection and exhibit less clinical symptoms than other ethnicities living under similar conditions, and a neighbouring ethnic group, the Dogon, in Mali. Our results indicate that DCs are semi-activated upon malaria exposure in vitro, including enhanced migratory capacity, partial up-regulation of co-stimulatory markers and no IL-12, which may lead to inappropriate T-cell priming. We also observed that DCs from the Fulani have a higher degree of activation than DCs from the Dogon upon malaria exposure in vivo. We hypothesize that this increased DC activation may be the reason for the relatively increased protection against malaria. Taken together, our findings suggest that improper DC activation may contribute to poor immunity in Malaria.
