Recrudescent Plasmodium berghei from pregnant mice displays enhanced binding to the placenta and induces protection in multigravida.
Pregnancy-associated malaria (PAM) is associated with placenta pathology and poor pregnancy outcome but the mechanisms that control the malaria parasite expansion in pregnancy are still poorly understood and not amenable for study in human subjects. Here, we used a set of new tools to re-visit an experimental mouse model of pregnancy-induced malaria recrudescence, BALB/c with chronic Plasmodium berghei infection. During pregnancy 60% of the pre-exposed primiparous females showed pregnancy-induced malaria recrudescence and we demonstrated that the recrudescent P. berghei show an unexpected enhancement of the adherence to placenta tissue sections with a marked specificity for CSA. Furthermore, we showed that the intensity of parasitemia in primigravida was quantitatively correlated with the degree of thickening of the placental tissue and up-regulation of inflammation-related genes such as IL10. We also confirmed that the incidence of pregnancy-induced recrudescence, the intensity of the parasitemia peak and the impact on the pregnancy outcome decreased gradually from the first to the third pregnancy. Interestingly, placenta pathology and fetal impairment were also observed at low frequency among non-recrudescent females. Together, the data raise the hypothesis that recrudescent P. berghei displays selected specificity for the placenta tissue enabling on one hand, the triggering of the pathological process underlying PAM and on the other hand, the induction of PAM protection mechanisms that are revealed in subsequent pregnancies. Thus, by exploiting P. berghei pregnancy-induced recrudescence, this experimental system offers a mouse model to study the susceptibility to PAM and the mechanisms of disease protection in multigravida.
Marinho
Claudio R F
CR
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Neres
Rita
R
Epiphanio
Sabrina
S
Gonçalves
Lígia A
LA
Catarino
Manuela Beirão
MB
Penha-Gonçalves
Carlos
C
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion; D004198:Disease Susceptibility; D004912:Erythrocytes / Q000166:cytology / Q000469:parasitology; D005260:Female; D005786:Gene Expression Regulation; D020073:Gravidity / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008288:Malaria / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000469:parasitology; D010920:Placenta / Q000098:blood supply / Q000469:parasitology* / Q000473:pathology; D010962:Plasmodium berghei / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D012008:Recurrence
D015415:Biomarkers; D049452:Green Fluorescent Proteins