Neonatal and maternal immunological responses to conserved epitopes within the DBL-gamma3 chondroitin sulfate A-binding domain of Plasmodium falciparum erythrocyte membrane protein 1

Autor: Peter G. Kremsner, Kim Brustoski, Martin Kramer, Ulrike Möller, Adrian J. F. Luty
Rok vydání: 2005
Předmět:
Zdroj: Infection and Immunity, 73, 12, pp. 7988-95
Infection and Immunity, 73, 7988-95
ISSN: 0019-9567
Popis: Plasmodium falciparumerythrocyte membrane protein 1 (PfEMP1) mediates the adherence ofP. falciparum-infected erythrocytes to placental syncytiotrophoblasts via interactions with chondroitin sulfate A (CSA), a characteristic of pregnancy-associated malaria. Pregnancy-associated malaria predicts increased susceptibility of newborns to malaria, and it is postulated that transplacental passage of parasite antigen induces immune regulatory activity in the neonate. We wished to examine the immune responsiveness to a CSA-binding domain of PfEMP1, the DBL-γ3 domain, in cord and maternal venous blood obtained from pregnancies with various histories ofP. falciparuminfection. We assessed in vitro T-cell cytokine and plasma immunoglobulin G (IgG) and IgM responses to four peptides corresponding to highly conserved regions of a DBL-γ3 domain common to central African parasite isolates. The presence of placentalP. falciparuminfection at delivery was associated with elevated frequencies of DBL-γ3 peptide-specific CD3+interleukin-10-positive T cells in cord blood, while treatment and clearance of infection prior to delivery was associated with elevated frequencies of CD3+gamma interferon-positive T cells. DBL-γ3 peptide-specific IgM antibodies were detected in 12 of 60 (20%) cord plasma samples from those born to mothers withP. falciparuminfection during pregnancy. Consistent with polyclonal anti-PfEMP1 antibody responses that are associated with protection against pregnancy-associated malaria, the presence of maternal IgG antibodies with specificity for one of the DBL-γ3 peptides showed a parity-dependent profile. These data demonstrate that peptides corresponding to conserved regions of the DBL-γ3 domain of PfEMP1 are immunogenic inP. falciparum-infected mothers and their offspring.
Databáze: OpenAIRE