Accumulation of CD4 and CD8 T Cells in Placenta of Malaria Infected Mice Induces the Expression of Hypoxia Inducible Factor-1α (HIF-1α) and Low Birth Weight (LBW) of the Fetus

Background: Placental malaria involves the sequestration of infected erythrocytes and infiltration of monocytes, helper T cells (CD4), cytotoxic T cells (CD8) as well as T-cell intracellular antigen-1 (TIA-1) in placental intervillous space. These may interferes the nutrient and oxygen transport, causing placental hypoxia and insufficiency that may affect the fetal growth. This study aimed to prove whether the infiltration of lymphocytes in placental malaria mice increases the expression of HIF-1α thus causes fetal Low Birth Weight (LBW). Methods: Nine pregnant BALB/c mice that infected with Plasmodium berghei ANKA strain on day 9 post mating were used as treatment group and 8 non infected pregnant mice were used as control group. The mice were sacrificed on day 18 post mating; then the fetus was weighed individually and the placentas were isolated separately. Expression of CD4, CD8 and HIF-1α were counted by immunohistochemistry using CD4 monoclonal Ab (Santa cruz, sc-59031 CD4) and CD 8 monoclonal Ab (NeoMarker RM-9116-S0) as well as anti-HIF-1α antibody (H1α67) ChIP Grade from Abcam. Results: There was a higher expression of CD8, CD4 and HIF-1α in infected placenta compare to normal placenta. Analysis using Structural Equation Modeling (SEM) showed expression CD8 and CD4 caused an increase expression of HIF-1α in placenta (t ≥1.96). Expression of HIF-1α caused low fetal weight (t ≥1.96). Conclusion: In placental malaria, the expression of CD4 and CD8 induce placental hypoxia characterized by increased expression of HIF-1α that causes LBW.