Malaria-Induced Murine Pregnancy Failure: Distinct Roles for IFN-γ and TNF

Poovassery, Jayakumar; Sarr, Demba; Smith, George S.; Nagy, Tamás; Moore, Julie M.

doi:10.4049/jimmunol.0901669

Cited by 47 publications

(102 citation statements)

References 51 publications

(79 reference statements)

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“…In addition to TNF-␣, other proinflammatory cytokines, such as IFN-␥, have been implicated in spontaneous abortion in humans (46). Similarly, murine models developed in an attempt to induce pregnancy failure through malaria infection point to systemic increases in TNF-␣ and IFN-␥ production as a cause of abortions (47,48). In our model system, we did not observe an increase in abortion or reabsorption due to systemic TNF-␣ or IFN-␥ production.…”

Section: Discussionmentioning

confidence: 51%

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

et al. 2014

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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.

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Section: Discussionmentioning

confidence: 51%

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

et al. 2014

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“…The proinflammatory cytokines IL-12 and IFN-␥ and cytotoxic CD8 ϩ T cells have been reported to play a crucial role in development of liver injury during P. berghei NK65 infection (18)(19)(20). Moreover, Poovassery et al demonstrated that pregnancy loss induces production of the proinflammatory cytokines IFN-␥ and tumor necrosis factor alpha in pregnant mice infected with Plasmodium chabaudi (38). These findings indicate that development of liver injury and placental pathology are associated with enhanced production of proinflammatory cytokines in pregnant IMϩNK mice.…”

Section: Discussionmentioning

confidence: 99%

Development of Severe Pathology in Immunized Pregnant Mice Challenged with Lethal Malaria Parasites

et al. 2013

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b Pregnant women are highly susceptible to malaria infection because of their low immunity and are at increased risk of maternal illness or death, in addition to spontaneous abortion, stillbirth, premature delivery, and low birth weight. However, the detailed pathogenesis of maternal malaria remains unclear. In this study, we evaluated a mouse model that shows similar severe pathological features of pregnant women during Plasmodium falciparum infection and investigated the pathogenesis of maternal malaria. Pregnant mice immunized by infection with an attenuated parasite, Plasmodium berghei XAT, were more susceptible to virulent P. berghei NK65 challenge/infection than were nonpregnant mice and showed high levels of parasitemia and a poor pregnancy outcome associated with placental pathology, such as accumulation of parasitized red blood cells, in the late phase of pregnancy. Notably, the pregnant immune mice challenged/infected with P. berghei NK65 developed liver injury associated with microvesicular fatty infiltration in late pregnancy. The pathological features were similar to acute fatty liver of pregnancy. Higher levels of gamma interferon and nitric oxide (NO) were found in plasma from pregnant immune mice infected with P. berghei NK65 than in plasma from nonpregnant mice. These findings suggest that development of liver injury and placental pathology in pregnant immune mice challenged/infected with P. berghei NK65 is accompanied by enhanced production of proinflammatory cytokines. Malaria is the most devastating parasitic disease of humans in tropical and subtropical regions, resulting in an estimated 0.6 to 1 million deaths per year (1). The populations at greatest risk of developing severe pathology are children under the age of 5 years and pregnant women in areas where Plasmodium falciparum is endemic (2-4). Every year, approximately 50 million women living in areas where malaria is endemic become pregnant. An estimated 10,000 of these women and 200,000 of their fetuses or infants die annually as a result of malaria during pregnancy (1, 2). Malaria during pregnancy is a major public health problem in areas of endemicity, especially in Africa.People living in regions where malaria is endemic acquire protective immunity against malaria parasites and often show asymptomatic infection. However, women are highly susceptible to malaria infection because of their low immunity during pregnancy and are at increased risk of maternal illness or death (5, 6). Malaria during pregnancy, in addition to maternal illness or death, is implicated in the occurrence of spontaneous abortion, stillbirth, premature delivery, and low birth weight (6). Recently, it has been demonstrated that pregnant mice infected with lethal Plasmodium berghei parasites show a feature similar to placental pathology and subsequently poor pregnancy outcome (7,8).Cerebral malaria (CM) or respiratory distress syndrome has been reported to be an infrequent but relevant cause of maternal death in women living in an area of sub-Saharan Africa where m...

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“…Other procoagulant mediators, including tumor necrosis factor α (39,40), cysteine proteinase (41), interferon-γ (40), asinterleukin-1 (42) and vascular permeability factor (43), are regarded as indirect procoagulants as they initiate coagulation by inducing TF in endothelial cells and monocytes (44). In addition, natural apoptosis may contribute to thrombogenesis in AL via the release of microparticles from the damaged leukemic Table II.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of D-dimer and lactate dehydrogenase plasma levels in patients with relapsed acute leukemia

Wang

Yang

2016

Oncology Letters

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Abstract. Despite the outstanding advances made over the past decade regarding our knowledge of acute leukemia (AL), relapsed AL remains to be associated with a dismal prognosis. A better understanding of AL relapse and monitoring of the D-dimer and lactate dehydrogenase (LDH) plasma levels following chemotherapy may aid clinicians in determining whether relapse may occur in the subsequent phases of the disease. The present study evaluated D-dimer and LDH levels in 204 patients with relapsed AL. Data were collected at the initial onset of AL, at complete remission (CR) and in patients with relapsed AL. D-dimer plasma levels were significantly increased in patients with initial AL and in patients with relapsed AL (P=0.005 and P=0.007, respectively) but not in those with CR. LDH levels were significantly increased in AL patients at the initial onset of disease and at relapse compared with patients achieving CR, irrespective of cell type. Plasma prothrombin time, activated partial thromboplastin time and fibrinogen levels were not significantly different across patients (with the exception of acute promyelocytic leukemia patients) at the initial onset, relapsed AL or CR. Routine hematological parameters (white blood cell count, hemoglobin, platelet count) were significantly different at the initial onset of AL (P=0.002, P<0.001 and P=0.001, respectively) and during relapsed AL (P=0.009, P=0.003 and P<0.001, respectively) compared with patients achieving CR, suggesting an association between D-dimer, LDH and relapsed AL. These results also indicate that determination of D-dimer and LDH levels may be useful for predicting the probability of relapse during chemotherapy, but should also be combined with routine hematological parameters.

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Malaria-Induced Murine Pregnancy Failure: Distinct Roles for IFN-γ and TNF

Cited by 47 publications

References 51 publications

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

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

Development of Severe Pathology in Immunized Pregnant Mice Challenged with Lethal Malaria Parasites

Evaluation of D-dimer and lactate dehydrogenase plasma levels in patients with relapsed acute leukemia

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