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  • 1.
    Badolati, Isabella
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Sverremark-Ekström, Eva
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    van der Heiden, Marieke
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Th9 cells in allergic diseases: A role for the microbiota?2020In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 91, no 4, article id e12857Article in journal (Refereed)
    Abstract [en]

    Since their discovery about 10 years ago, Th9 cells have been increasingly linked to allergic pathologies. Within this review, we summarize the current knowledge on associations between Th9 cells and allergic diseases and acknowledge Th9 cells as important targets in future treatment of allergic diseases. However, until today, it is not fully understood how these Th9 cell responses are modulated. We describe current literature suggesting that these Th9 cell responses might be stimulated by microbial species such as Staphylococcus aureus and Candida albicans, while on the other hand, microbial and dietary compounds such as retinoic acid (RA), butyrate and vitamin D show suppressive capacity on allergy-related Th9 responses. By reviewing this recent research, we provide new insights into the modulating capacity of the microbiota on Th9 cell responses. Consequently, microbial and dietary factors may be used as innovative tools to target Th9 cells in the treatment of allergic diseases. However, further research is needed to elucidate the mechanisms behind these interactions in order to translate this knowledge into clinical allergy settings.

  • 2.
    Björkander, Sofia
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Heidari-Hamedani, Ghazal
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Bremme, K.
    Gunnarsson, I.
    Holmlund, Ulrika
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Peripheral Monocyte Expression of the Chemokine Receptors CCR2, CCR5 and CXCR3 is Altered at Parturition in Healthy Women and in Women with Systemic Lupus Erythematosus2013In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 77, no 3, p. 200-212Article in journal (Refereed)
    Abstract [en]

    Monocytes are precursors of macrophages and recruited to the uterus throughout pregnancy to perform important immunological functions. In this study, we hypothesized that pregnant women have reduced peripheral monocyte expression of chemokine receptors and alterations in PBMC responses to microbial stimuli as an adaption to pregnancy and that these changes are less pronounced in women with autoimmunity. We therefore investigated the chemokine receptor expression, migratory behaviour and responses to microbial stimulation of peripheral monocytes from pregnant women at parturition (n=13) and from non-pregnant women (n=9). In addition, we compared healthy pregnant women with women suffering from SLE (n=5), a condition with pronounced systemic inflammation increasing the risk for pregnancy complications. We demonstrate that peripheral monocytes are affected by pregnancy with reduced percentages of CCR2+, CCR5+ and CXCR3+ monocytes of both classical (CD16) and inflammatory (CD16+) subsets and that the trophoblast-secreted chemokine CCL2/MCP-1 recruited monocytes of both subsets in vitro. Further, PBMCs from pregnant women had a divergent response to microbial stimulation with lower CCL5/RANTES and higher CCL2/MCP-1 secretion compared with non-pregnant women. In addition, pregnant women had lower basal PBMC-secretion of CCL5/RANTES and higher basal secretion of IL-10 and CCL2/MCP-1. Interestingly, the women with SLE responded similar to pregnancy as did healthy women with lower percentages of CCR2+, CCR5+ and CXCR3+ monocytes. However, they had increased expression of CCR5 on CD16+ monocytes and heightened PBMC-secretion of CCL5/RANTES. In conclusion, our data indicate that monocyte chemokine receptor expression and the chemokine milieu during pregnancy are tightly regulated to support pregnancy.

  • 3. Bolad, Ahmed
    et al.
    Farouk, Salah E.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Israelsson, Elisabeth
    Dolo, Amagana
    Doumbo, Ogobara K.
    Nebié, Issa
    Maiga, Boubacar
    Kouriba, Bourema
    Luoni, Gaia
    Sirima, Bienveu S.
    Distinct interethnic differences in IgG class/subclass and IgM antibody responses to malaria antigens but not in IgG responses to non-malarial antigens in sympatric tribes living in West Africa2005In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 61, no 4, p. 380-386Article in journal (Refereed)
    Abstract [en]

    The well-established relative resistance to malaria observed in the Fulani as compared with other sympatric tribes in West Africa has been attributed to their higher levels of serum immunoglobulin (Ig) G antibodies to malarial antigens. In this study, we confirm and extend the previous findings by analyses of the levels of IgM, IgG and IgG subclasses of anti-malarial antibodies in asymptomatic individuals of different sympatric tribes in Burkina Faso (Fulani/Mossi) and Mali (Fulani/Dogon). The Fulani showed significantly higher median concentrations of anti-malarial IgG and IgM antibodies than the sympatric tribes at both locations. Although the overall subclass pattern of antibodies did not differ between the tribes, with IgG1 and IgG3 as dominant, the Fulani showed consistently significantly higher levels of these subclasses as compared with those of the non-Fulani individuals. No significant differences were seen in the levels of total IgG between the tribes, but the Fulani showed significantly higher levels of total IgM than their neighbours in both countries. While the antibody levels to some nonmalarial antigens showed the same pattern of differences seen for antibody levels to malaria antigens, no significant such differences were seen with antibodies to other nonmalarial antigens. In conclusion, our results show that the Fulani in two different countries show higher levels of anti-malarial antibodies than sympatric tribes, and this appears not to be a reflection of a general hyper-reactivity in the Fulani.

  • 4. Bolad, Ahmed
    et al.
    Farouk, Salah E.
    Modiano, David
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Israelsson, Elisabeth
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Dolo, Amagana
    Doumbo, Ogobara K.
    Nebié, Issa
    Maiga, Boubacar
    Kouriba, Bourema
    Luoni, Gaia
    Sirima, Bienveu Sodiomon
    Distinct interethnic differences in IgG class/subclass and IgM antibody responses to malaria antigens but not in IgG responses to non-malarial antigens in sympatric tribes living in West Africa2005In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 61, no 4, p. 380-386Article in journal (Refereed)
    Abstract [en]

    The well-established relative resistance to malaria observed in the Fulani ascompared with other sympatric tribes in West Africa has been attributed totheir higher levels of serum immunoglobulin (Ig) G antibodies to malarialantigens. In this study, we confirm and extend the previous findings by analysesof the levels of IgM, IgG and IgG subclasses of anti-malarial antibodies inasymptomatic individuals of different sympatric tribes in Burkina Faso(Fulani/Mossi) and Mali (Fulani/Dogon). The Fulani showed significantlyhigher median concentrations of anti-malarial IgG and IgM antibodies thanthe sympatric tribes at both locations. Although the overall subclass pattern ofantibodies did not differ between the tribes, with IgG1 and IgG3 as dominant,the Fulani showed consistently significantly higher levels of these subclasses ascompared with those of the non-Fulani individuals. No significant differenceswere seen in the levels of total IgG between the tribes, but the Fulani showedsignificantly higher levels of total IgM than their neighbours in both countries.While the antibody levels to some nonmalarial antigens showed the same patternof differences seen for antibody levels to malaria antigens, no significant suchdifferences were seen with antibodies to other nonmalarial antigens. In conclusion,our results show that the Fulani in two different countries show higherlevels of anti-malarial antibodies than sympatric tribes, and this appears not tobe a reflection of a general hyper-reactivity in the Fulani.

  • 5.
    Calla-Magariños, Jacqueline
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Gimenez, A.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Fernandez, Carmen
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    An alkaloid extract of Evanta, traditionally used as anti-Leishmania agent in Bolivia, inhibits cellular proliferation and interferon-g production in polyclonally activated cells2009In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 69, no 3, p. 251-258Article in journal (Refereed)
    Abstract [en]

    Traditional medicine and scientific studies have shown that the raw extract ofEvanta [Galipea longiflora, Angostura longiflora (Krause) Kallunki] exhibits antileishmanialactivity. We hypothesized that the healing observed when usingthis plant might not only be due to the direct action on the parasite, but possiblyto a parallel effect on the host immune response to the parasite involvedin the healing process. We show here that an alkaloid extract of Evanta (AEE)directly killed the parasite already at a dose of 10 lg ⁄ ml, but at this low concentration,AEE did not have a major effect on viability and proliferation ofeukaryotic cells. The whole extract was also found to be stronger than 2-phenylquinoline,the most prominent alkaloid in AEE. AEE was not directlystimulating B or T cells or J774 macrophages. However, it interfered with theactivation of both mouse and human T cells, as revealed by a reduction of invitro cellular proliferation and interferon-gamma (IFN-c) production. The effectwas more evident when the cells were pretreated with AEE and subsequentlystimulated with the polyclonal T-cell activators Concanavalin A and anti-CD3.Taken together, our results suggest that Evanta have a direct leishmanicidaleffect and due to the effect on IFN-c production it might contribute to controlthe chronic inflammatory reaction that characterize Leishmania infectionpathology, but in vivo studies are necessary to corroborate this finding.

  • 6.
    Calla-Magariños, Jacqueline
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute.
    Quispe, T.
    Giménez, A.
    Freysdottir, J.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute.
    Fernández, Carmen
    Stockholm University, Faculty of Science, The Wenner-Gren Institute.
    Quinolinic Alkaloids from Galipea longiflora Krause Suppress Production of Proinflammatory Cytokines in vitro and Control Inflammation in vivo upon Leishmania Infection in Mice2013In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 77, no 1, p. 30-38Article in journal (Refereed)
    Abstract [en]

    An antileishmanial activity of quinolinic alkaloids from Galipea longiflora Krause, known as Evanta, has been demonstrated. We have previously shown that, apart from its leishmanicidal effect, in vitro pretreatment of spleen cells with an alkaloid extract of Evanta (AEE) interfered with the proliferation and interferon-γ production in lymphocytes polyclonally activated either with concanavalin A or anti-CD3. In the present study, we investigated if AEE could interfere with antigen-specific lymphocyte activation. We found that in vitro and in vivo treatment reduced recall lymphocyte responses, as measured by IFN-γ production (55% and 63% reduction compared to untreated cells, respectively). Apart from IFN-γ, the production of IL-12 and TNF was also suppressed. No effects were observed for meglumine antimoniate (SbV), the conventional drug used to treat leishmaniasis. When mice infected with Leishmania braziliensis promastigotes in the hind footpad were treated with AEE, the dynamics of the infection changed and the footpath thickness was efficiently controlled. The parasite load was also reduced but to a lesser extent than upon treatment with SbV. Combined treatment efficiently controlled both the thickness and parasite load as smaller lesions during the entire course of the infection were seen in the mice treated with AEE plus SbV compared with AEE or SbV alone. We discuss the benefits of combined administration of AEE plus SbV.

  • 7.
    Calla-Magariños, Jacqueline
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Quispe, Teddy
    Giménez, Alberto
    Freysdottir, Jona
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Fernández, Carmen
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Quinolinic alkaloids from Galipea longiflora suppress inflammatory cytokine production in vitro and control inflammatory reaction in vivo upon Leishmania infectionIn: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083Article in journal (Refereed)
    Abstract [en]

    An antileishmanial activity of quinolinic alkaloids from Galipea longiflora Krause, known as Evanta, has been demonstrated. We have previously shown that, apart from its leishmanicidal effect, in vitro pretreatment of spleen cells with an alkaloid extract of Evanta (AEE) interfered with the proliferation and interferon-g production in lymphocytes polyclonally activated either with concanavalin A or anti-CD3. In the present study, we investigated if AEE could interfere with antigen-specific lymphocyte activation. We found that in vitro and in vivo treatment reduced recall lymphocyte responses, as measured by IFN-g production (55 % and 63 % reduction compared to untreated cells, respectively). Apart from IFN-g, the production of IL-12 and TNF were also suppressed. No effects were observed for meglumine antimoniate (SbV), the conventional drug used to treat leishmaniasis. When mice infected with Leishmania braziliensis promastigotes in the hind footpad were treated with AEE, the dynamics of the infection changed and the footpath thickness was efficiently controlled. The parasite load was also reduced but to a lesser extent than upon treatment with SbV. Combined treatment efficiently controlled both the thickness and parasite load since smaller lesions during the entire course of the infection were seen in the mice treated with AEE plus SbV compared with AEE or SbV alone. We discuss the benefits of combined administration of AEE plus SbV.

  • 8. Cherif, M. K.
    et al.
    Sanou, G. S.
    Maiga, B.
    Israelsson, E.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Ouedraogo, A. L.
    Bougouma, E. C.
    Diarra, A.
    Ouedraogo, A.
    Ouattara, A. S.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Dolo, A.
    Cavanagh, D. R.
    Theisen, M.
    Modiano, D.
    Sirima, S. B.
    Nebie, I.
    Fc gamma RIIa Polymorphism and Anti-Malaria-Specific IgG and IgG Subclass Responses in Populations Differing in Susceptibility to Malaria in Burkina Faso2012In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 75, no 6, p. 606-613Article in journal (Refereed)
    Abstract [en]

    Fc?RIIa is known to be polymorphic; and certain variants are associated with different susceptibilities to malaria. Studies involving the Fulani ethnic group reported an ethnic difference in Fc?RIIa-R131H genotype frequencies between the Fulani and other sympatric groups. No previous studies have addressed these questions in Burkina Faso. This study aimed to assess the influence of Fc?RIIa-R131H polymorphism on anti-falciparum malaria IgG and IgG subclass responses in the Fulani and the Mossi ethnic groups living in Burkina Faso. Healthy adults more than 20 years old belonging to the Mossi or the Fulani ethnic groups were enrolled for the assessment of selected parasitological, immunological and genetic variables in relation to their susceptibility to malaria. The prevalence of the Plasmodium falciparum infection frequency was relatively low in the Fulani ethnic group compared to the Mossi ethnic group. For all tested antigens, the Fulani had higher antibody levels than the Mossi group. In both ethnic groups, a similar distribution of Fc?RIIa R131H polymorphism was found. Individuals with the R allele of Fc?RIIa had higher antibody levels than those with the H allele. This study confirmed that malaria infection affected less the Fulani group than the Mossi group. Fc?RIIa-R131H allele distribution is similar in both ethnic groups, and higher antibody levels are associated with the Fc?RIIa R allele compared to the H allele.

  • 9.
    Djerbi, M.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Malinowski, M. M.
    Yagita, H.
    Zhivotovsky, B.
    Grandien, A.
    Participation of FLIP, RIP and Bcl-x(L) in fas-mediated T-cell death2007In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 66, no 4, p. 410-421Article in journal (Refereed)
    Abstract [en]

    Apart from the conventional Fas signalling pathway, alternative pathways including the mitochondrial caspase-dependent and RIP-mediated cell death routes have been proposed to operate during Fas-mediated cell death. To evaluate the contribution of different Fas signalling pathways, mice overexpressing FLIPL, Bcl-x(L), a kinase-deficient form of RIP (RIP Delta kin) or combinations thereof were generated by retroviral gene transfer of haematopoietic stem cells. Such mice did not show overt abnormalities in haematopoietic development, defects in thymic deletion, accumulation of double-negative T cells or signs of autoimmunity. Fas-mediated death of mitogen-activated T cells was caspase dependent and could be blocked by FLIPL overexpression only with the minor involvement of Bcl-x(L) or RIP Delta kin inhibitable pathways. Fas-mediated death of resting CD4(+) and CD8(+) T cells was mainly caspase dependent but could only partly be blocked by FLIPL overexpression. Both Bcl-x(L) or RIP Delta kin expression resulted in partial protection of CD8(+) T cells against Fas-mediated cell death. These results indicate that yet uncharacterized signalling pathways from the Fas receptor are critically involved in lymphoproliferative and autoimmune disease observed in lpr mice and autoimmune lymphoproliferative syndrome patients.

  • 10. Fernández Mastache, Elena
    et al.
    Lindroth, Karin
    Stockholm University, Faculty of Science, The Wenner-Gren Institute.
    González Fernández, África
    Fernández, Carmen
    Somatic hypermutation of Ig genes is affected differently by failures in apoptosis caused by disruption of Fas (lpr mutation) or by over-expression of Bcl-22006In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 63, no 6, p. 420-429Article in journal (Refereed)
    Abstract [en]

    The effects of the two main apoptotic pathways on the somatic hypermutation process were analysed. Transgenic mice carrying the V(kappa)Ox1-J(kappa)5 rat transgene were crossed with Fas-deficient lpr mice or with mice overexpressing the Bcl-2 protein. The transgenic V(kappa)Ox1 segment and the endogenous J(H)4-C-mu Ig intron from Peyer's patches germinal centre B cells were sequenced to study the intrinsic somatic hypermutation process without the skewing effects of specific antigen selection. The lpr/ox mice displayed, in both regions, a high level of mutations with a normal pattern of substitutions. On the contrary, the bcl-2/ox mice displayed a lower level of mutations with an altered pattern, showing a decreased mutational rate in the intrinsic hotspots of the V(kappa)Ox1 gene. Our results suggest that the lpr mutation does not have a direct effect on the somatic hypermutation process, but rather on the negative selection of B cells in the germinal centres, leading to the accumulation of recurrent mutations. In contrast, Bcl-2 overexpression might influence the somatic hypermutational process either by altering the incorporation of mutations or by enhancing the repair mechanism(s). The present work supports the hypothesis that both apoptotic pathways, Fas and Bcl-2, play distinct roles in the germinal centre reactions.

  • 11.
    Hansson, Monika
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Abedi-Valugerdi, Manuchehr
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Mercuric chloride induces a strong immune activation, but does not accelerate the development of dermal fibrosis in tight-skin 1 (Tsk 1) mice2004In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 59, no 5, p. 469-477Article in journal (Refereed)
    Abstract [en]

    In susceptible mice, mercuric chloride induces a systemic autoimmune disease characterized by increased serum levels of immunoglobulin (Ig) G1 and IgE, production of anti-nucleolar autoantibodies (ANolA) and formation of renal IgG deposits. We have previously hypothesized that mercury confers more adverse immunological effects on those mouse strains, which are genetically prone to develop spontaneous autoimmune diseases than on normal strains. In this study, we tested our hypothesis in tight skin 1 (Tsk1/+) mice, a murine model for human scleroderma. As a support for our hypothesis, we observed that in Tsk1/+ mice, B cells were spontaneously hyperactive and that treatment with mercury induced a strong immune/autoimmune response in these mice, but not in their non-Tsk (+/+) littermates. This response was characterized by the formation of high numbers of splenic IgG1, IgG2b and IgG3 antibody-secreting cells, increased serum levels of IgE, production of IgG1 antibodies against single-stranded DNA (ssDNA), trinitrophenol (TNP) as well as thyroglobulin and the development of renal IgG1 deposits. Neither Tsk1/+ mice nor F1 hybrid crosses between this strain, and mercury susceptible B10.S (H-2s) were able to produce IgG1-ANolA in response to mercury. Moreover, mercury-induced immune activation in Tsk1/+ was not able to potentiate the progression of skin fibrosis in this strain. Thus, exposure to mercury accelerates the immune dysregulation, but not the development of skin fibrosis in Tsk1/+ mice.

  • 12.
    Maiga, Bakary
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases/Faculty of Medicine, Pharmacy and Odonto, Stomatology, Bamako, Mali.
    Dolo, A
    Touré, O
    Dara, V
    Tapily, A
    Campino, S
    Sepulveda, N
    Corran, P
    Rockett, K
    Clark, T G
    Troye Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Doumbo, O K
    Fc gamma Receptor IIa-H131R Polymorphism and Malaria Susceptibility in Sympatric Ethnic Groups, Fulani and Dogon of Mali2014In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, no 1, p. 43-50Article in journal (Refereed)
    Abstract [en]

    It has been previously shown that there are some interethnic differences in susceptibility to malaria between two sympatric ethnic groups of Mali, the Fulani and the Dogon. The lower susceptibility to Plasmodium falciparum malaria seen in the Fulani has not been fully explained by genetic polymorphisms previously known to be associated with malaria resistance, including haemoglobin S (HbS), haemoglobin C (HbC), alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Given the observed differences in the distribution of FcγRIIa allotypes among different ethnic groups and with malaria susceptibility that have been reported, we analysed the rs1801274-R131H polymorphism in the FcγRIIa gene in a study of Dogon and Fulani in Mali (n = 939). We confirm that the Fulani have less parasite densities, less parasite prevalence, more spleen enlargement and higher levels of total IgG antibodies (anti-CSP, anti-AMA1, anti-MSP1 and anti-MSP2) and more total IgE (P < 0.05) compared with the Dogon ethnic group. Furthermore, the Fulani exhibit higher frequencies of the blood group O (56.5%) compared with the Dogon (43.5%) (P < 0.001). With regard to the FcγRIIa polymorphism and allele frequency, the Fulani group have a higher frequency of the H allele (Fulani 0.474, Dogon 0.341, P < 0.0001), which was associated with greater total IgE production (P = 0.004). Our findings show that the FcγRIIa polymorphism might have an implication in the relative protection seen in the Fulani tribe, with confirmatory studies required in other malaria endemic settings.

  • 13. Nasr, A.
    et al.
    Iriemenam, N. C.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Arnot, D.
    Theander, T. G.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Giha, H. A.
    ElGhazali, G.
    Pattern of Pre-existing IgG Subclass Responses to a Panel of Asexual Stage Malaria Antigens Reported During the Lengthy Dry Season in Daraweesh, Sudan2011In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 74, no 4, p. 390-396Article in journal (Refereed)
    Abstract [en]

    The anti-malarial IgG immune response during the lengthy and dry season in areas of low malaria transmission as in Eastern Sudan is largely unknown. In this study, ELISA was used for the measurement of pre-existing total IgG and IgG subclasses to a panel of malaria antigens, MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231. The results showed that the antibody responses were predominantly age dependent, antigen specific, and their lifespan was at least 5-6 month long. Generally, the IgG3 was most abundant IgG subclass, and the most recognized antigen was Pf332-C231. Furthermore, the correlation between the levels of IgG subclasses was strongest between IgG1 and IgG3, which were more predictive to the total IgG levels. Finally, the response pattern of each of the IgG subclasses to the different test antigens that were spanning the dry season and the correlation between these responses were described in details for the first time.

  • 14.
    Nasr, A.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Iriemenam, N.C.
    Troye-Blomberg, M.
    Giha, H.A.
    Balogun, H.A.
    Osman, O.F.
    Montgomery, S.M
    ElGhazali, G.
    Berzins, K.
    Fc gamma Receptor IIa (CD32) Polymorphism and Antibody responses to Asexual Blood-stage Antigens of Plasmodium falciparum Malaria in Sudanese Patients2007In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 66, no 1, p. 87-96Article in journal (Refereed)
  • 15.
    Nyakeriga, Alice
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Williams, Thomas
    Marsh, Kevin
    Wambua, Sammy
    Perlmann, Hedvig
    Perlmann, Peter
    Grandien, Alf
    Troye-Blomberg, Marita
    Cytokine mRNA expression and iron status in children in a malaria endemic area2005In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 61, no 4, p. 370-375Article in journal (Refereed)
    Abstract [en]

    Iron deficiency has been reported to affect both malaria pathogenesis and cell-mediated immune responses; however, it is unclear whether the protection afforded by iron deficiency is mediated through direct effects on the parasite, through immune effector functions or through both. We have determined cytokine mRNA expression levels in 59 children living in a malaria endemic area on the coast of Kenya who we selected on the basis of their biochemical iron status. Real-time quantitative reverse transcriptase polymerase chain reaction analysis of cytokine mRNA levels of peripheral blood mononuclear cells (PBMC) obtained from these children showed an association between interleukin-4 (IL-4) mRNA levels and all the biochemical indices of iron that we measured. Furthermore, IL-10 mRNA was higher in parasite blood smear-positive children than in blood smear-negative children irrespective of their iron status. This study suggests that IL-4 expression by PBMC may be affected by iron status.

  • 16.
    Qazi, Mousumi Rahman
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Abedi, M. R.
    Nelson, Buck Dean
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    DePierre, J. W.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Abedi-Valugerdi, Manuchehr
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Characterization of the Hepatic and Splenic Immune Status and Immunoglobulin Synthesis in Aged Male Mice Lacking the Peroxisome Proliferator-Activated Receptor-Alpha (PPAR alpha)2011In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 73, no 3, p. 198-207Article in journal (Refereed)
    Abstract [en]

    It is now well established that the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR alpha) is expressed in different types of immune cells and plays a pivotal role in the regulation of age-related production of inflammatory cytokines. However, the role(s) of this receptor in the regulation of immune cell homoeostasis in ageing non-lymphoid and lymphoid organs has not yet been resolved. We examine this issue here by evaluating the hepatic and splenic immune status and immunoglobulin (Ig) production in male PPAR alpha-null mice and their wild-type littermates at one and 2 years of age. In comparison with the age-matched control animals, PPAR alpha-null mice exhibited age-related elevations in the numbers of total, as well as of phenotypically distinct subpopulations of intrahepatic immune cells (IHIC) and splenocytes. Moreover, at 2 years of age, these alterations in hepatic immune cells were accompanied by significant increases in hepatic levels of the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma), in combination with the development of hepatic inflammatory loci containing mixtures of leucocytes. Alterations in splenocytes of old PPAR alpha-null mice were also accompanied by increases in cellularity of both white and red pulps of the spleen. Furthermore, these same animals exhibited pronounced increases in the numbers of splenic plasma cells and enhanced production of Ig of different isotypes, including IgG1, IgG2a and IgE. Thus, our findings indicate that upon ageing, PPAR alpha plays a crucial role in regulating the total numbers, compositions and functions of immune cells in both lymphoid and non-lymphoid immune organs of mice.

  • 17.
    Troye-Blomberg, Marita
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Arama, Charles
    Quin, Jaclyn
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. CEITEC Masaryk University, Czech Republic.
    Bujila, Ioana
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Public Health Agency of Sweden, Sweden.
    Östlund Farrants, Ann-Kristin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?2020In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 92, no 4, article id e12932Article, review/survey (Refereed)
    Abstract [en]

    There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.

  • 18.
    van der Heiden, Marieke
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nopp, Anna
    Brandström, Josef
    Carvalho-Queiroz, Claudia
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nilsson, Caroline
    Sverremark-Ekström, Eva
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    A pilot study towards the immunological effects of omalizumab treatment used to facilitate oral immunotherapy in peanut-allergic adolescents2021In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 93, no 4, article id e13005Article in journal (Refereed)
    Abstract [en]

    Anti-IgE treatments, such as omalizumab, have shown promising effects in allergy treatment. Our previous work has shown that individualized omalizumab treatment (OT) allows a safe initiation and rapid up-dosing of peanut oral immunotherapy (OIT) in peanut-allergic adolescents. However, the broader immunological effects of this OT are incompletely understood. In this pilot study, we longitudinally followed the total B- and T-cell immunity during OT, using flow cytometry, ELISpot and ELISA. Peripheral blood mononuclear cells (PBMCs) and plasma were collected from participants (n = 17) at several timepoints during treatment, before starting OT (baseline), prior to starting OIT during OT (start OIT) and at maintenance dose OIT prior to OT reduction (maintenance). OT did not affect the total B-cell compartment over treatment time, but our results suggest an association between the OT dosage scheme and the B-cell compartment. Further, in vitro polyclonal T-cell activation at the different timepoints suggests a cytokine skewing towards the Th1 phenotype at the expense of Th2- and Th9-related cytokines during treatment. No differences in the frequencies or phenotype of regulatory T cells (Tregs) over treatment time were observed. Finally, plasma chemokine levels were stable over treatment time, but suggest elevated gut homing immune responses in treatment successes during the treatment as compared to treatment failures. The novel and explorative results of this pilot study help to improve our understanding on the immunological effects of OT used to facilitate OIT and provide guidance for future immunological investigation in large clinical trials.

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