Acquired Immune Responses to Plasmodium falciparum Merozoite Surface Protein-1 in the Human Fetus

Abstract

Infants born in areas of stable malaria transmission are relatively protected against severe morbidity and high density Plasmodium falciparum blood-stage infection. This protection may involve prenatal sensitization and immunologic reactivity to malaria surface ligands that participate in invasion of red cells. We examined cord blood T and B cell immunity to P. falciparum merozoite surface protein-1 (MSP-1) in infants born in an area of stable malaria transmission in Kenya. T cell cytokine responses to the C-terminal 19-kDa fragment of MSP-1 (MSP-119) were detected in 24 of 92 (26%) newborns (4–192 IFN-γ and 3–88 IL-4-secreting cells per 106/cord blood lymphocytes). Peptide epitopes in the N-terminal block 3 region of MSP-1 also drove IFN-γ and/or IL-13 production. There was no evidence of prenatal T cell sensitization to liver-stage Ag-1. A total of 5 of 86 (6%) newborns had cord blood anti-MSP-119 IgM Abs, an Ig isotype that does not cross the placenta and is therefore of fetal origin. The frequency of neonatal B cell sensitization was higher than that indicated by serology alone, as 5 of 27 (18%) cord blood samples contained B cells that produced IgG when stimulated with MSP-119 in vitro. Neonatal B cell IgG responses were restricted to the Q-KNG allele of MSP-119, the major variant in this endemic area, whereas T cells responded to all four MSP-119 alleles evaluated. In utero sensitization to MSP-1 correlated with the presence of malaria parasites in cord blood (χ2 = 20, p < 0.0001). These data indicate that prenatal sensitization to blood-stage Ags occurs in infants born in malaria endemic areas.

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea

“…Similar phenomena have been shown for helminths and malarial parasitic infections in pregnancy, where pathogen‐specific T cell responses induced in utero have long‐term negative consequences for the infants' susceptibility and development of immune responses to these parasites 41, 42, 43, 44, 45, 46, 47, 48, 49. Accordingly, in‐utero infection with cytomegalovirus (CMV) has been found to result in in‐utero activation of fetal CMV T cell responses that, compared to adult responses, are ‘functionally exhausted’, with a limited capacity to control CMV replication 50, 51.…”

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth

“…Furthermore, separate populations of FOXP3 IL-10 (Tr1) and TGF-b (Th3) producing induced CD4 1 Treg have also been described, the former of which have been implicated in a regulatory role in malaria infection [20]. Several human studies suggest a role for malaria-specific IL-10 production in cord blood [7,[21][22][23]. Human natural Treg defined as CD4 1 CD25 hi were found to be increased in PM exposed cord blood samples.…”

“…A number of immunological studies have assessed the effect of PM on the newborn's immune function, supporting prenatal T-cell sensitization to malaria Ag [6,7]. These have demonstrated low level reactivity to schizont extract, and certain blood stage Ag, and lack of reactivity to liver stage Ag [7][8][9][10][11].…”

“…These have demonstrated low level reactivity to schizont extract, and certain blood stage Ag, and lack of reactivity to liver stage Ag [7][8][9][10][11]. Healthy adults living in malaria endemic regions generally have low level cellular reactivity to P. falciparum Ag despite lifelong exposure to parasites [12][13][14].…”

Hemoglobinas humanas: hipótese malária ou efeito materno?

“…45 Esta proteção pode envolver sensibilização pré-natal e reação imunológica em receptores de membranas que participam do processo de invasão parasitária. 46 Os anticorpos antimaláricos específicos produzidos pelo feto são desconhecidos, mas podem ser limitados devido ao repertório das células B fetais reduzidos quando comparado ao de adultos. Como resultado, é possível que no feto seja produzido um número limitado de anticorpos para antígenos maláricos.…”