MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

Abstract

e Malaria is a widespread infectious disease caused by the parasite Plasmodium. During pregnancy, malaria infection leads to a range of complications that can affect both the mother and fetus, including stillbirth, infant mortality, and low birth weight. In this study, we utilized a mouse model of placental malaria (PM) infection to determine the importance of the protein MyD88 in the host immune response to Plasmodium during pregnancy. Initially, we demonstrated that Plasmodium berghei NK65GFP adhered to placental tissue via chondroitin sulfate A and induced PM in mice with a C57BL/6 genetic background. To evaluate the involvement of MyD88 in the pathology of PM, we performed a histopathological analysis of placentas obtained from MyD88 ؊/؊ and wild-type (WT) mice following infection on the 19th gestational day. Our data demonstrated that the detrimental placental alterations observed in the infected mice were correlated with the expression of MyD88. Moreover, in the absence of this protein, production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-␣) was significantly reduced in the infected mice. More importantly, in contrast to fetuses from infected WT mice, which exhibited a reduction in body weight, the fetuses from infected MyD88 ؊/؊ mice did not display significant weight loss compared to their noninfected littermates. In addition, we observed a decrement of maternal care associated with malaria infection, which was attenuated in the MyD88-deficient mice. Collectively, the results of this study illustrate the pivotal importance of the MyD88 signaling pathway in the pathogenesis of placental malaria, thus presenting new possibilities for targeting MyD88 in therapeutic interventions.

Integrated Proteomics Reveals Apoptosis-related Mechanisms Associated with Placental Malaria*

“…on G13 with 1 ϫ 10 5 iRBCs. G13 was determined as the optimal time point for the infection to enable the analysis of the malaria pathological features during the course of pregnancy and in the developing fetus, as infection at an earlier stage would not allow the pregnancy to reach its term, which is consistent with previous report (16). Pregnant mice underwent cesarean sections on G19, and their placentas were collected for histopathological analysis and protein extraction.…”

“…Mice and Parasites-In this study, an experimental model of PM female C57BL/six pregnant (16). C57BL/6 (Wild-Type [WT]) from the animal breeding facility of the Institute of Biomedical Sciences at the University of Sã o Paulo (ICB/USP) was used with ages from 8 to 10 weeks, which were bred and kept in a constant light-dark cycle (12 h/12 h) in conventional housing at animal facility of the ICB/USP Department of Parasitology.…”

“…Pregnancy Monitoring and Experimental Infection-Detection of a vaginal plug and measurement of the body weight were combined to set the gestation time, as previously described (16). Females (2 or 3) were placed with one male for 24 h and examined for the presence of the vaginal plug.…”

Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes

“…We used a PM experimental model to ascertain whether IL-1 and the inflammasome activity are involved in the PM pathogenesis (9,22). On gestational day 13 (G13), C57BL/6 pregnant mice were infected with P. berghei (Pb) NK65 GFP .…”

Differential roles of inflammation and apoptosis in initiation of mid-gestational abortion in malaria-infected C57BL/6 and A/J mice

“…In this model, MyD88-dependent inflammatory response [19], oxidative stress, apoptosis [20, 21], angiogenic dysregulation, and complement component C5a [22] have been proposed as mediators of fetal compromise. Additionally, trophoblast phagocytosis of red blood cells is associated with pregnancy loss in mice infected with P. chabaudi AS [23] as well as P. berghei [24].…”