Pregnancy outcome and placenta pathology in Plasmodium berghei ANKA infected mice reproduce the pathogenesis of severe malaria in pregnant women.
Pregnancy-associated malaria (PAM) is expressed in a range of clinical complications that include increased disease severity in pregnant women, decreased fetal viability, intra-uterine growth retardation, low birth weight and infant mortality. The physiopathology of malaria in pregnancy is difficult to scrutinize and attempts were made in the past to use animal models for pregnancy malaria studies. Here, we describe a comprehensive mouse experimental model that recapitulates many of the pathological and clinical features typical of human severe malaria in pregnancy. We used P. berghei ANKA-GFP infection during pregnancy to evoke a prominent inflammatory response in the placenta that entails CD11b mononuclear infiltration, up-regulation of MIP-1 alpha chemokine and is associated with marked reduction of placental vascular spaces. Placenta pathology was associated with decreased fetal viability, intra-uterine growth retardation, gross post-natal growth impairment and increased disease severity in pregnant females. Moreover, we provide evidence that CSA and HA, known to mediate P. falciparum adhesion to human placenta, are also involved in mouse placental malaria infection. We propose that reduction of maternal blood flow in the placenta is a key pathogenic factor in murine pregnancy malaria and we hypothesize that exacerbated innate inflammatory responses to Plasmodium infected red blood cells trigger severe placenta pathology. This experimental model provides an opportunity to identify cell and molecular components of severe PAM pathogenesis and to investigate the inflammatory response that leads to the observed fetal and placental blood circulation abnormalities.
Neres
Rita
R
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Marinho
Claudio R F
CR
Gonçalves
Lígia A
LA
Catarino
Manuela Beirão
MB
Penha-Gonçalves
Carlos
C
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation; D008288:Malaria; D051379:Mice; D010922:Placenta Diseases / Q000469:parasitology* / Q000473:pathology; D021041:Placental Circulation; D010962:Plasmodium berghei; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic; D011256:Pregnancy Outcome