Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy

Samad Ibitokou; Mayke Oesterholt; Laurent Brutus; Sophie Borgella; Carine Agbowaï; Sèm Ezinmègnon; John Lusingu; Christentze Schmiegelow; Achille Massougbodji; Philippe Deloron; Marita Troye-Blomberg; Stefania Varani; Adrian J F Luty; Nadine Fievet

doi:10.1371/journal.pone.0049621

Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy

Samad Ibitokou, Mayke Oesterholt, Laurent Brutus, Sophie Borgella, Carine Agbowaï, Sèm Ezinmègnon, John Lusingu, Christentze Schmiegelow, Achille Massougbodji, Philippe Deloron, Marita Troye-Blomberg, Stefania Varani, Adrian J F Luty, Nadine Fievet

14 Citations (Scopus)

Abstract

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.

Original language	English
Journal	P L o S One
Volume	7
Issue number	12
Pages (from-to)	e49621
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0049621
Publication status	Published - 11 Dec 2012

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1371/journal.pone.0049621

Cite this

Ibitokou, S., Oesterholt, M., Brutus, L., Borgella, S., Agbowaï, C., Ezinmègnon, S., Lusingu, J., Schmiegelow, C., Massougbodji, A., Deloron, P., Troye-Blomberg, M., Varani, S., Luty, A. J. F., & Fievet, N. (2012). Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy. P L o S One, 7(12), e49621. https://doi.org/10.1371/journal.pone.0049621

@article{991364bfc9014a2c9bba0b549bd257d9,

title = "Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy",

abstract = "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.",

author = "Samad Ibitokou and Mayke Oesterholt and Laurent Brutus and Sophie Borgella and Carine Agbowa{\"i} and S{\`e}m Ezinm{\`e}gnon and John Lusingu and Christentze Schmiegelow and Achille Massougbodji and Philippe Deloron and Marita Troye-Blomberg and Stefania Varani and Luty, {Adrian J F} and Nadine Fievet",

year = "2012",

month = dec,

day = "11",

doi = "10.1371/journal.pone.0049621",

language = "English",

volume = "7",

pages = "e49621",

journal = "P L o S One",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "12",

}

TY - JOUR

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 - 2012/12/11

Y1 - 2012/12/11

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

SN - 1932-6203

VL - 7

SP - e49621

JO - P L o S One

JF - P L o S One

IS - 12

ER -

Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this