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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 Africa
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
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2005 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 61, no 4, 380-386 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
2005. Vol. 61, no 4, 380-386 p.
Keyword [en]
*IMMUNOGLOBULIN G *MALARIA *PROTOZOAN diseases *ANTIGENS *IMMUNITY
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:su:diva-23516DOI: 10.1111/j.1365-3083.2005.01587.xOAI: oai:DiVA.org:su-23516DiVA: diva2:192441
Note
Part of urn:nbn:se:su:diva-320Available from: 2004-12-20 Created: 2004-12-20 Last updated: 2017-12-13Bibliographically approved
In thesis
1. T cell and antibody responses in Plasmodium falciparum malaria and their relation to disease susceptibility
Open this publication in new window or tab >>T cell and antibody responses in Plasmodium falciparum malaria and their relation to disease susceptibility
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Malaria antigen-induced polarization of T cells into effectors Th1 and/or Th2 cells and their subsequent release of cytokines is known to affect antibody production. This thesis includes studies on early innate responses to the parasite, with a focus on γδT cells, and acquired specific responses in African sympatric ethnic tribes. In the last part of this thesis, a method for enrichment for the asexual blood stages of P. falciparum and their use in in vitro T-cell studies is presented.

To investigate mechanisms involved in parasite growth inhibition by γδT cells, an in vitro system was set up using blood stage parasites co-cultured with differently treated γδT cells. The results showed that Vγ9/δ2+ γδT cells inhibited the in vitro growth of P. falciparum parasites whereas CD4+ and CD8+ T cells did not. This inhibition was positively correlated with the expression of cytolytic molecules in the cell lines tested. Anti-granulysin antibodies reversed γδT cell-mediated inhibition, suggesting a role for granulysin in the parasite growth inhibition. Thus, our data suggest that Vγ9/δ2+ γδT cells inhibit the parasite growth by a granulysin-exocytosis dependent cytotoxic pathway that needs perforin.

To study the humoral responses and their relation to Th1/Th2 cytokine profiles, antibody levels, numbers of cytokine-producing cells and spleen rates were measured in two sympatric tribes living in Mali, the Fulani and the Dogon. Our results revealed significantly elevated malaria-specific IgG and IgE antibody levels and spleen rates in the Fulani compared to the Dogon. The Fulani exhibited elevated numbers of both IL-4 and IFN-γ-producing cells, a typical profile seen of CD1-restricted NKT cells. This together with the higher spleen rates and elevated anti-malarial antibodies suggests a role of CD1-restricted cells in the different responses seen between these tribes.

To investigate whether such responses were specifically confined to malaria or a reflection of a generally activated immune system, total levels of IgG and of IgM as well as IgG antibodies to non-malarial antigens were examined in the Fulani in Burkina Faso and Mali. The results showed that the Fulani consistently mounted stronger malaria-specific IgG, IgG1, IgG3 and IgM responses. Total IgM levels were significantly higher in the Fulani than the non-Fulani, whereas total IgG did not differ between the two tribes. While IgG levels to some non-malarial antigens were significantly higher in the Fulani, no such differences were seen in the responses to several other non-malarial antigens suggesting that the Fulani are not generally hyper-reactive and that other specific factors are of importance for their higher malaria resistance.

Finally, a new method to enrich for early and late asexual blood stages of P. falciparum parasite from a single parasite culture was developed, using a 3-step centrifugation procedure. Such enriched parasite fractions beside other malaria-parasite antigen preparations were used in an in vitro system to analyse T-cell responses in malaria-exposed and non-exposed donors. Such analysis revealed significant proliferative cell response and CD4+ T cell expansion to whole-cell parasite antigens, but not to acellular parasite fractions, in the malaria-exposed as compared to the non-exposed ones. Our data suggest that natural infection preferentially leads to formation of memory cells against certain antigen expressed in live parasites.

Malaria antigen-induced polarization of T cells into effectors Th1 and/or Th2 cells and their subsequent release of cytokines is known to affect antibody production. This thesis includes studies on early innate responses to the parasite, with a focus on γδT cells, and acquired specific responses in African sympatric ethnic tribes. In the last part of this thesis, a method for enrichment for the asexual blood stages of P. falciparum and their use in in vitro T-cell studies is presented.

To investigate mechanisms involved in parasite growth inhibition by γδT cells, an in vitro system was set up using blood stage parasites co-cultured with differently treated γδT cells. The results showed that Vγ9/δ2+ γδT cells inhibited the in vitro growth of P. falciparum parasites whereas CD4+ and CD8+ T cells did not. This inhibition was positively correlated with the expression of cytolytic molecules in the cell lines tested. Anti-granulysin antibodies reversed γδT cell-mediated inhibition, suggesting a role for granulysin in the parasite growth inhibition. Thus, our data suggest that Vγ9/δ2+ γδT cells inhibit the parasite growth by a granulysin-exocytosis dependent cytotoxic pathway that needs perforin.

To study the humoral responses and their relation to Th1/Th2 cytokine profiles, antibody levels, numbers of cytokine-producing cells and spleen rates were measured in two sympatric tribes living in Mali, the Fulani and the Dogon. Our results revealed significantly elevated malaria-specific IgG and IgE antibody levels and spleen rates in the Fulani compared to the Dogon. The Fulani exhibited elevated numbers of both IL-4 and IFN-γ-producing cells, a typical profile seen of CD1-restricted NKT cells. This together with the higher spleen rates and elevated anti-malarial antibodies suggests a role of CD1-restricted cells in the different responses seen between these tribes.

To investigate whether such responses were specifically confined to malaria or a reflection of a generally activated immune system, total levels of IgG and of IgM as well as IgG antibodies to non-malarial antigens were examined in the Fulani in Burkina Faso and Mali. The results showed that the Fulani consistently mounted stronger malaria-specific IgG, IgG1, IgG3 and IgM responses. Total IgM levels were significantly higher in the Fulani than the non-Fulani, whereas total IgG did not differ between the two tribes. While IgG levels to some non-malarial antigens were significantly higher in the Fulani, no such differences were seen in the responses to several other non-malarial antigens suggesting that the Fulani are not generally hyper-reactive and that other specific factors are of importance for their higher malaria resistance.

Finally, a new method to enrich for early and late asexual blood stages of P. falciparum parasite from a single parasite culture was developed, using a 3-step centrifugation procedure. Such enriched parasite fractions beside other malaria-parasite antigen preparations were used in an in vitro system to analyse T-cell responses in malaria-exposed and non-exposed donors. Such analysis revealed significant proliferative cell response and CD4+ T cell expansion to whole-cell parasite antigens, but not to acellular parasite fractions, in the malaria-exposed as compared to the non-exposed ones. Our data suggest that natural infection preferentially leads to formation of memory cells against certain antigen expressed in live parasites.

Malaria antigen-induced polarization of T cells into effectors Th1 and/or Th2 cells and their subsequent release of cytokines is known to affect antibody production. This thesis includes studies on early innate responses to the parasite, with a focus on γδT cells, and acquired specific responses in African sympatric ethnic tribes. In the last part of this thesis, a method for enrichment for the asexual blood stages of P. falciparum and their use in in vitro T-cell studies is presented.

To investigate mechanisms involved in parasite growth inhibition by γδT cells, an in vitro system was set up using blood stage parasites co-cultured with differently treated γδT cells. The results showed that Vγ9/δ2+ γδT cells inhibited the in vitro growth of P. falciparum parasites whereas CD4+ and CD8+ T cells did not. This inhibition was positively correlated with the expression of cytolytic molecules in the cell lines tested. Anti-granulysin antibodies reversed γδT cell-mediated inhibition, suggesting a role for granulysin in the parasite growth inhibition. Thus, our data suggest that Vγ9/δ2+ γδT cells inhibit the parasite growth by a granulysin-exocytosis dependent cytotoxic pathway that needs perforin.

To study the humoral responses and their relation to Th1/Th2 cytokine profiles, antibody levels, numbers of cytokine-producing cells and spleen rates were measured in two sympatric tribes living in Mali, the Fulani and the Dogon. Our results revealed significantly elevated malaria-specific IgG and IgE antibody levels and spleen rates in the Fulani compared to the Dogon. The Fulani exhibited elevated numbers of both IL-4 and IFN-γ-producing cells, a typical profile seen of CD1-restricted NKT cells. This together with the higher spleen rates and elevated anti-malarial antibodies suggests a role of CD1-restricted cells in the different responses seen between these tribes.

To investigate whether such responses were specifically confined to malaria or a reflection of a generally activated immune system, total levels of IgG and of IgM as well as IgG antibodies to non-malarial antigens were examined in the Fulani in Burkina Faso and Mali. The results showed that the Fulani consistently mounted stronger malaria-specific IgG, IgG1, IgG3 and IgM responses. Total IgM levels were significantly higher in the Fulani than the non-Fulani, whereas total IgG did not differ between the two tribes. While IgG levels to some non-malarial antigens were significantly higher in the Fulani, no such differences were seen in the responses to several other non-malarial antigens suggesting that the Fulani are not generally hyper-reactive and that other specific factors are of importance for their higher malaria resistance.

Finally, a new method to enrich for early and late asexual blood stages of P. falciparum parasite from a single parasite culture was developed, using a 3-step centrifugation procedure. Such enriched parasite fractions beside other malaria-parasite antigen preparations were used in an in vitro system to analyse T-cell responses in malaria-exposed and non-exposed donors. Such analysis revealed significant proliferative cell response and CD4+ T cell expansion to whole-cell parasite antigens, but not to acellular parasite fractions, in the malaria-exposed as compared to the non-exposed ones. Our data suggest that natural infection preferentially leads to formation of memory cells against certain antigen expressed in live parasites.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi, 2004. 74 p.
Keyword
P. falciparum, Malaria, Granulysin, Fulani, Schizont
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:su:diva-320 (URN)91-7265-987-4 (ISBN)
Public defence
2005-01-21, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00
Opponent
Supervisors
Available from: 2004-12-20 Created: 2004-12-20Bibliographically approved

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