Trends in Parasitology
ReviewOf mice and women: rodent models of placental malaria
Section snippets
Placental malaria: Plasmodium falciparum and the extended family
Infection with Plasmodium falciparum parasites during pregnancy can have serious adverse consequences for the mother and not least her baby and is estimated to be the cause of up to 200 000 infant deaths per year [1]. The marked placental accumulation of infected erythrocytes (IEs), which is the central feature of malaria during pregnancy (Box 1), has been known for at least a century [2], but a detailed understanding of the pathogenesis of placental malaria (PM) and the role of immunity in
Malaria during pregnancy in non-immune rodents
P. berghei infections are uniformly fatal in non-immune pregnant and non-pregnant rodents, but the course of P. berghei infection is accelerated in pregnant mice 12, 13, whereas it appears to be more variable in rats 14, 15. Early infection of pregnant mice generally causes abortion, though pregnancy often proceeds after later infection, yet with clear signs of pathology in the mother as well as the offspring 9, 12, 16. Complications include foetal resorption, intrauterine growth retardation,
Malaria in immune, pregnant mice
In 1980, van Zon et al. published a study [30] which differed from all its predecessors in its focus on mice that had been rendered immune to P. berghei infection prior to mating. Clearly, this approach much better simulates the situation facing primigravidae in areas of intense parasite transmission, and the authors proposed their model as a convenient tool to study why previously acquired protective immunity to P. falciparum infection fails during pregnancy. They found that if virgin mice
Placental malaria in humans
Whereas non-immune animals dominate studies of malaria in pregnant rodents, there are only a few studies of P. falciparum infection during pregnancy in women with limited or no pre-existing anti-malarial immunity [36]. Overall, studies from low-endemicity settings report that infections are symptomatic with substantial peripheral parasitaemia and that pregnant women are at increased risk of malaria compared to men and non-pregnant women. If untreated, such infections often progress to severe
Human reality and murine simulations of it
Today, there is ample evidence that VSAs are both important determinants of the pathogenesis of P. falciparum infection and major targets of naturally acquired protective immunity to malaria in general, and PM in particular 46, 58. However, the important studies by van Zon et al. on P. berghei pre-immunized pregnant mice 34, 35 were conducted at a time when the importance of VSA-specific immunity in malaria was not generally appreciated, let alone its relevance to PM. Nevertheless, clinically
Concluding remarks, and the way forward
That pregnant women are at increased risk of malaria has been known for more than a century, and malaria in pregnant rodents has been studied for at least fifty years. Nevertheless, the relevance of mouse models to understanding the pathogenesis of, and immune response to, P. falciparum malaria is a continuing point of contention [69]. Such scepticism seems particularly justified where important antigens are absent from model parasites, as is the case for PfEMP1 in general and VAR2CSA in
Disclosure statement
We declare to have no actual or potential conflicts of interest including any financial, personal or other relationships with other people or organizations within three (3) years of beginning the work submitted that could inappropriately influence (bias) the contents of the present manuscript.
Acknowledgements
The financial support for our research from BioMalPar/EviMalaR, the Danish Medical Research Council, the Fundação para a Ciência e Tecnologia, Programa POCI 2010 and FEDER, and Rigshospitalet is gratefully acknowledged. John Steinbeck (and Mestas and Hughes) and Raymond Carver (and Haruki Murakami) are acknowledged for inspiring the title of this paper and the heading of Box 1, respectively.
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Cited by (32)
Host immunity to Plasmodium infection: Contribution of Plasmodium berghei to our understanding of T cell-related immune response to blood-stage malaria
2023, Parasitology InternationalCitation Excerpt :On the other hand, infection of the same mouse strain with P. berghei NK65 strain induces lung pathology, and liver injury [6,7]. Infection with P. berghei strains is also used as experimental model of pregnancy-associated malaria [8–11]. P. berghei XAT, X ray-attenuated strain derived from P. berghei NK65 strain [12,13], is suitable for investigations of protective immune responses against live-attenuated Plasmodium parasites.
Maternal and fetal outcome of pregnancy in Swiss mice infected with Plasmodium berghei ANKA<sup>GFP</sup>
2019, Reproductive ToxicologyCitation Excerpt :Murine models with different parasites have been used to evaluate malaria in pregnancy, as P. chabaudi, P. vinckei, P. yoelii and P. berghei [19]. Among them, the murine models of malaria using P. berghei were recapitulating some features of malaria in pregnancy caused by the P. falciparum in humans, it is important to mention that P. berghei-infected mice reproduced the pathogenesis of placental malaria in pregnant human [19,21–23]. These features include low birth weight, higher susceptibility to infection in pregnant animals, IUGR, decreased fetal viability and alterations on the placenta tissue [19,21,22].
Differential roles of inflammation and apoptosis in initiation of mid-gestational abortion in malaria-infected C57BL/6 and A/J mice
2015, PlacentaCitation Excerpt :These important contributions notwithstanding, the precise molecular and cellular mechanisms that lead to placental failure and fetal compromise must still be identified. Using a murine model of PM during late pregnancy, previous studies have demonstrated the ability of Plasmodium berghei ANKA to recapitulate the characteristic features of human PM including infected red blood cell (iRBC) adherence to placental tissue [17]. In pregnant BALB/c mice infected with P. berghei ANKA at gestation day 13, necrosis, maternal blood sinusoid constriction, syncytiotrophoblast hyperplasia, distension of perivascular space, and mononuclear cell infiltration are observed in the term placenta [18].
From mice to women: The conundrum of immunity to infection during pregnancy
2013, Journal of Reproductive ImmunologyCitation Excerpt :A seminal study revealed that binding of Plasmodium falciparum infected erythrocytes to placental chondriotin sulphate A (CSA) results sequestration of the parasite to the feto-maternal interface (Fried et al., 2006). A number of African rodent malaria species were identified between 1948 and 1960 and two main strains have been extensively studied; Plasmodium chabaudi and Plasmodium berghei (Hviid et al., 2010; Stephens et al., 2012). Human malaria is characterized by cyclical fever and schizogony wherein the parasites invade particular erythrocyte populations.
Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis
2012, Hormones and BehaviorCitation Excerpt :In malaria endemic areas, susceptibility to malarial infections is increased during pregnancy and is higher among primiparous (i.e., females that are in their first pregnancy) than multiparous (i.e., females that have had multiple pregnancies) females. Females are more susceptible to infection during the first pregnancy because they are immunologically naïve to the parasite adhesion proteins (i.e., they do not possess anti-adhesion antibodies) that are expressed in the placenta during pregnancy (Fried et al., 1998; Hviid et al., 2010; Rogerson et al., 2007). Increased susceptibility to infection among pregnant females is attributed to both increased parasites sequestered in the placenta and pregnancy-associated suppression of inflammatory responses caused by hormonal changes during pregnancy (Rogerson et al., 2007).