A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria.
In Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF) and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-04-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3075246?pdf=render |
| _version_ | 1818194839676649472 |
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| author | Chanaki Amaratunga Tatiana M Lopera-Mesa Nathaniel J Brittain Rushina Cholera Takayuki Arie Hisashi Fujioka Jeffrey R Keefer Rick M Fairhurst |
| author_facet | Chanaki Amaratunga Tatiana M Lopera-Mesa Nathaniel J Brittain Rushina Cholera Takayuki Arie Hisashi Fujioka Jeffrey R Keefer Rick M Fairhurst |
| author_sort | Chanaki Amaratunga |
| collection | DOAJ |
| description | In Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF) and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever, and the almost complete lack of severe disease. This resistance has previously been attributed in part to poor parasite growth in HbF-containing red blood cells (RBCs). A specific role for maternal immune IgG in infant resistance to malaria has been hypothesized but not yet identified.We found that P. falciparum parasites invade and develop normally in fetal (cord blood, CB) RBCs, which contain up to 95% HbF. However, these parasitized CB RBCs are impaired in their binding to human microvascular endothelial cells (MVECs), monocytes, and nonparasitized RBCs--cytoadherence interactions that have been implicated in the development of high parasite densities and the symptoms of malaria. Abnormal display of the parasite's cytoadherence antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1) on CB RBCs accounts for these findings and is reminiscent of that on HbC and HbS RBCs. IgG purified from the plasma of immune Malian adults almost completely abolishes the adherence of parasitized CB RBCs to MVECs.Our data suggest a model of malaria protection in which HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized RBCs in the first few months of life. In highly malarious areas of Africa, an infant's contemporaneous expression of HbC or HbS and development of an immune IgG repertoire may effectively reconstitute the waning protective effects of HbF and maternal immune IgG, thereby extending the malaria resistance of infancy into early childhood. |
| first_indexed | 2024-12-12T01:08:40Z |
| format | Article |
| id | doaj.art-1ec8f3ce6e7541679428b70da5439344 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T01:08:40Z |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1ec8f3ce6e7541679428b70da54393442022-12-22T00:43:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1479810.1371/journal.pone.0014798A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria.Chanaki AmaratungaTatiana M Lopera-MesaNathaniel J BrittainRushina CholeraTakayuki ArieHisashi FujiokaJeffrey R KeeferRick M FairhurstIn Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF) and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever, and the almost complete lack of severe disease. This resistance has previously been attributed in part to poor parasite growth in HbF-containing red blood cells (RBCs). A specific role for maternal immune IgG in infant resistance to malaria has been hypothesized but not yet identified.We found that P. falciparum parasites invade and develop normally in fetal (cord blood, CB) RBCs, which contain up to 95% HbF. However, these parasitized CB RBCs are impaired in their binding to human microvascular endothelial cells (MVECs), monocytes, and nonparasitized RBCs--cytoadherence interactions that have been implicated in the development of high parasite densities and the symptoms of malaria. Abnormal display of the parasite's cytoadherence antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1) on CB RBCs accounts for these findings and is reminiscent of that on HbC and HbS RBCs. IgG purified from the plasma of immune Malian adults almost completely abolishes the adherence of parasitized CB RBCs to MVECs.Our data suggest a model of malaria protection in which HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized RBCs in the first few months of life. In highly malarious areas of Africa, an infant's contemporaneous expression of HbC or HbS and development of an immune IgG repertoire may effectively reconstitute the waning protective effects of HbF and maternal immune IgG, thereby extending the malaria resistance of infancy into early childhood.http://europepmc.org/articles/PMC3075246?pdf=render |
| spellingShingle | Chanaki Amaratunga Tatiana M Lopera-Mesa Nathaniel J Brittain Rushina Cholera Takayuki Arie Hisashi Fujioka Jeffrey R Keefer Rick M Fairhurst A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria. PLoS ONE |
| title | A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria. |
| title_full | A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria. |
| title_fullStr | A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria. |
| title_full_unstemmed | A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria. |
| title_short | A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria. |
| title_sort | role for fetal hemoglobin and maternal immune igg in infant resistance to plasmodium falciparum malaria |
| url | http://europepmc.org/articles/PMC3075246?pdf=render |
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