Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy
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Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy. / Ibitokou, Samad; Oesterholt, Mayke; Brutus, Laurent; Borgella, Sophie; Agbowaï, Carine; Ezinmègnon, Sèm; Lusingu, John; Schmiegelow, Christentze; Massougbodji, Achille; Deloron, Philippe; Troye-Blomberg, Marita; Varani, Stefania; Luty, Adrian J F; Fievet, Nadine.
In: P L o S One, Vol. 7, No. 12, 2012, p. e49621.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy
AU - Ibitokou, Samad
AU - Oesterholt, Mayke
AU - Brutus, Laurent
AU - Borgella, Sophie
AU - Agbowaï, Carine
AU - Ezinmègnon, Sèm
AU - Lusingu, John
AU - Schmiegelow, Christentze
AU - Massougbodji, Achille
AU - Deloron, Philippe
AU - Troye-Blomberg, Marita
AU - Varani, Stefania
AU - Luty, Adrian J F
AU - Fievet, Nadine
PY - 2012
Y1 - 2012
N2 - Sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM) is scarce. We conducted a longitudinal, prospective study, both in Benin and Tanzania, including ~1000 pregnant women in each site with systematic follow-up at scheduled antenatal visits until delivery. We used ex vivo flow cytometry to identify peripheral blood mononuclear cell (PBMC) profiles that are associated with PAM and anaemia, determining the phenotypic composition and activation status of PBMC in selected sub-groups with and without PAM both at inclusion and at delivery in a total of 302 women. Both at inclusion and at delivery PAM was associated with significantly increased frequencies both of B cells overall and of activated B cells. Infection-related profiles were otherwise quite distinct at the two different time-points. At inclusion, PAM was associated with anaemia, with an increased frequency of immature monocytes and with a decreased frequency of regulatory T cells (Treg). At delivery, infected women presented with significantly fewer plasmacytoid dendritic cells (DC), more myeloid DC expressing low levels of HLA-DR, and more effector T cells (Teff) compared to uninfected women. Independent associations with an increased risk of anaemia were found for altered antigen-presenting cell frequencies at inclusion, but for an increased frequency of Teff at delivery. Our findings emphasize the prominent role played by B cells during PAM whenever it arises during pregnancy, whilst also revealing signature changes in other circulating cell types that, we conclude, primarily reflect the relative duration of the infections. Thus, the acute, recently-acquired infections present at delivery were marked by changes in DC and Teff frequencies, contrasting with infections at inclusion, considered chronic in nature, that were characterized by an abundance of immature monocytes and a paucity of Treg in PBMC.
AB - Sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM) is scarce. We conducted a longitudinal, prospective study, both in Benin and Tanzania, including ~1000 pregnant women in each site with systematic follow-up at scheduled antenatal visits until delivery. We used ex vivo flow cytometry to identify peripheral blood mononuclear cell (PBMC) profiles that are associated with PAM and anaemia, determining the phenotypic composition and activation status of PBMC in selected sub-groups with and without PAM both at inclusion and at delivery in a total of 302 women. Both at inclusion and at delivery PAM was associated with significantly increased frequencies both of B cells overall and of activated B cells. Infection-related profiles were otherwise quite distinct at the two different time-points. At inclusion, PAM was associated with anaemia, with an increased frequency of immature monocytes and with a decreased frequency of regulatory T cells (Treg). At delivery, infected women presented with significantly fewer plasmacytoid dendritic cells (DC), more myeloid DC expressing low levels of HLA-DR, and more effector T cells (Teff) compared to uninfected women. Independent associations with an increased risk of anaemia were found for altered antigen-presenting cell frequencies at inclusion, but for an increased frequency of Teff at delivery. Our findings emphasize the prominent role played by B cells during PAM whenever it arises during pregnancy, whilst also revealing signature changes in other circulating cell types that, we conclude, primarily reflect the relative duration of the infections. Thus, the acute, recently-acquired infections present at delivery were marked by changes in DC and Teff frequencies, contrasting with infections at inclusion, considered chronic in nature, that were characterized by an abundance of immature monocytes and a paucity of Treg in PBMC.
U2 - 10.1371/journal.pone.0049621
DO - 10.1371/journal.pone.0049621
M3 - Journal article
C2 - 23239967
VL - 7
SP - e49621
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 12
ER -
ID: 43233759