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

Abstract

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.

High Degree of Parasitemia Induces Placental Hypoxia and Low Birth Weight

“…Karakteristik histopatologi pada malaria plasenta yaitu penebalan membran basal, infiltrasi monosit dalam ruang intervillous dari plasenta (intervillositis) (Sharma & Shukla, 2017), hal tersebut dapat meningkatkan hambatan transportasi oksigen melintasi plasenta (Hviid, 2010). Akumulasi sel-sel inflamasi dan eritrosit yang terinfeksi juga bisa menyebabkan hipoksia plasenta Terjadinya disfungsi plasenta secara langsung dapat mempengaruhi perkembangan janin dan menyebabkan FGR (Rahmah et al, 2019) Degradasi HIF-1α tidak terjadi pada kondisi hipoksia karena pada kondisi hipoksia tersebut konsentrasi oksigen pada sel rendah, sehingga proses-proses hidroksilasi yang membutuhkan oksigen tidak dapat terjadi. Tidak terjadinya hidroksilasi Pro402 dan Pro564 pada ODDD HIF-1α oleh PHD akan mengakibatkan pVHL tidak dapat berikatan pada HIF-1α.…”

Malaria in Pregnancy: From Placental Infection to Its Abnormal Development and Damage

“…Intervillositis in human- (Ordi et al, 1998;Rogerson et al, 2003b;Muehlenbachs et al, 2010) Mononuclear cells infiltration in mice- (Neres et al, 2008;Poovassery et al, 2009;Sarr et al, 2015;Rahmah et al, 2019) Lack of monocytes and macrophages accumulation in placentas of mice- (Poovassery and Moore, 2006;Sharma et al, 2016) Frontiers in Microbiology | www.frontiersin.org FIGURE 1 | Schematic representation of a healthy functional unit of the human placenta. The placenta is a specialized organ that is primarily involved in the exchange of metabolites between the mother and her fetus.…”