Peripheral Blood Mononuclear Cells Derived from Grand Multigravidae Display a Distinct Cytokine Profile in Response to P. falciparum Infected Erythrocytes

Abstract

Immunopathology of placental malaria is most significant in women in their first pregnancy especially in endemic areas, due to a lack of protective immunity to Plasmodium falciparum, which is acquired in successive pregnancies. In some studies (but not all), grand multigravidae (defined as 5 or more pregnancies, G5–7) are more susceptible to poor birth outcomes associated with malaria compared to earlier gravidities. By comparing peripheral cellular responses in primigravidae (G1), women in their second to fourth pregnancy (G2–4) and grand multigravidae we sought to identify key components of the dysregulated immune response. PBMC were exposed to CS2-infected erythrocytes (IE) opsonised with autologous plasma or unopsonised IE, and cytokine and chemokine secretion was measured. Higher levels of opsonising antibody were present in plasma derived from multigravid compared to primigravid women. Significant differences in the levels of cytokines and chemokines secreted in response to IE were observed. Less IL-10, IL-1β, IL-6 and TNF but more CXCL8, CCL8, IFNγ and CXCL10 were detected in G5–7 compared to G2–4 women. Our study provides fresh insight into the modulation of peripheral blood cell function and effects on the balance between host protection and immunopathology during placental malaria infection.

Innate immune responses to malaria-infected erythrocytes in pregnant women: Effects of gravidity, malaria infection, and geographic location

“…AUS and PNG_I groups were each divided into 15 primigravid and 15 multigravid women, whiles the PNG_N group constituted 11 primigravid and 15 multigravid women. (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) weeks] were significantly higher in Australian women compared to malaria-negative PNG women. Of the infected PNG women 17 had parasites detected by microscopy and PCR, while 13 had submicroscopic infection.…”

“…In a previous study from PNG, cytokine and chemokine secretion by peripheral blood mononuclear cells (PBMC) stimulated with VAR2CSA-expressing CS2-IE were reported to differ between multigravidae (2-4 pregnancies) and grand-multigravidae (5-7 pregnancies) [23]. However, it remains unclear whether the observed immune response was affected by lifetime malaria exposure or gravidity.…”

“…In 96-well round bottom plates, 2 x 10 5 viable cells/well were plated and rested at 37˚C for 1 hour. PBMC were then incubated with IE (6 x 10 5 per well), uRBC (6 x 10 5 per well) or PHA (2%), and supernatants were analysed after 48 hours [35,36]. PBMCs were tested in batches of 6-9 samples at a time, selected from across the different participant groups.…”

VAR2CSA-Mediated Host Defense Evasion of Plasmodium falciparum Infected Erythrocytes in Placental Malaria

“…Interestingly, a study performed in an area of low prevalence of malaria, revealed gravidity-dependent differences in the capacity of peripheral blood mononuclear cells (PBMCs) to produce cytokines and chemokines in response to pregnancy-specific IEs ( 86 ). Despite no differences in opsonic antibody levels, cellular immune responses differed between women in their second to fourth pregnancy (G2-4) and grand multigravida (G5-G7).…”

“…Despite no differences in opsonic antibody levels, cellular immune responses differed between women in their second to fourth pregnancy (G2-4) and grand multigravida (G5-G7). Indeed, more IL-10, IL-1β, IL-6, tumor necrosis factor (TNF) but less CXCL-8, CCL-8, IFNγ, and CXCL-10 were detected in G2-4 compared to G5-7, highlighting the modulation of immune cell function occurring during PM ( 86 ).…”