The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth.
Placental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign Ag. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analyzed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial Ag in utero results in the expansion of malaria-specific FOXP3(+) Treg and more generalized FOXP3(+) CD4(+) Treg in chronic and resolved PM, alongside increased Th1 pro-inflammatory responses (IFN-gamma, TNF-alpha, IFN-gamma:IL-10) in resolved PM infection only. These observations demonstrate a clear effect of exposure to malarial Ag in foetal life on the immune environment at birth, with a regulatory response dominating in the newborns with ongoing chronic PM, while those with resolved infection produce both regulatory and inflammatory responses. The findings might explain some of the adverse effects on the health of babies born to women with PM.
Flanagan
Katie L
KL
MRC Laboratories, Fajara, The Gambia. kflanagan@mrc.gm
Halliday
Alice
A
Burl
Sarah
S
Landgraf
Katja
K
Jagne
Ya Jankey
YJ
Noho-Konteh
Fatou
F
Townend
John
J
Miles
David J C
DJ
van der Sande
Marianne
M
Whittle
Hilton
H
Rowland-Jones
Sarah
S
D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000276:immunology* / Q000469:parasitology; D005315:Fetal Diseases / Q000276:immunology* / Q000469:parasitology; D005333:Fetus / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn / Q000097:blood / Q000276:immunology*; D018445:Infectious Disease Transmission, Vertical; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D016778:Malaria, Falciparum / Q000151:congenital / Q000196:embryology / Q000276:immunology*; D008297:Male; D018512:Parasitemia / Q000151:congenital / Q000196:embryology / Q000276:immunology*; D010922:Placenta Diseases / Q000276:immunology* / Q000469:parasitology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000469:parasitology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma