{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T04:50:27Z","timestamp":1769662227483,"version":"3.49.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although an important role for excessive proinflammatory cytokines in compromise of pregnancy has been established, an immunological basis for malaria-induced fetal loss remains to be demonstrated. In this study, the roles of IFN-\u03b3 and TNF in Plasmodium chabaudi AS-induced fetal loss in mice were directly investigated. Pregnant IFN-\u03b3\u2212\/\u2212 mice experienced a more severe course of infection compared with intact C57BL\/6 mice, characterized by high parasitemia, severe anemia, and marked weight loss. However, fetal loss was delayed in these mice relative to intact controls. Because IFN-\u03b3\u2212\/\u2212 mice exhibited sustained levels of plasma TNF, the role of this cytokine was examined. Whereas splenic tnf expression in C57BL\/6 mice was highest 3 days before peak parasitemia, increased placental expression relative to uninfected mice was sustained, indicating that locally produced TNF may be important in malaria-induced pregnancy failure. Indeed, Ab neutralization of TNF resulted in preservation of embryos until day 12 of gestation, at which point all embryos were lost in untreated mice. Histological analysis revealed that TNF ablation preserved placental architecture whereas placentae from untreated infected mice had widespread hemorrhage and placental disruption, with fibrin thrombi in some maternal blood sinusoids. Consistent with a role for cytokine-driven thrombosis in fetal loss, expression of procoagulant tissue factor was significantly increased in the placentae of infected C57BL\/6 mice but was reduced in mice treated with anti-TNF Ab. Together, these results suggest that IFN-\u03b3 contributes to malaria-induced fetal loss and TNF is a critical factor that acts by inducing placental coagulopathy.<\/jats:p>","DOI":"10.4049\/jimmunol.0901669","type":"journal-article","created":{"date-parts":[[2009,9,25]],"date-time":"2009-09-25T21:40:38Z","timestamp":1253914838000},"page":"5342-5349","source":"Crossref","is-referenced-by-count":44,"title":["Malaria-Induced Murine Pregnancy Failure: Distinct Roles for IFN-\u03b3 and TNF"],"prefix":"10.1093","volume":"183","author":[{"given":"Jayakumar S","family":"Poovassery","sequence":"first","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases"},{"name":"Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demba","family":"Sarr","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases"},{"name":"Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases"},{"name":"Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamas","family":"Nagy","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, University of Georgia , Athens, GA 30602"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie M","family":"Moore","sequence":"additional","affiliation":[{"name":"Center for Tropical and Emerging Global Diseases"},{"name":"Department of Infectious Diseases"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,10,15]]},"reference":[{"key":"2026012811274756100_R1","first-page":"2759","article-title":"Host response to malaria during pregnancy: placental monocyte recruitment is associated with elevated \u03b2 chemokine expression.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012811274756100_R2","first-page":"1530","article-title":"Plasmodium falciparum induces a Th1\/Th2 disequilibrium, favoring the Th1-type pathway, in the human placenta.","volume-title":"J. Infect. Dis.","year":"2001"},{"key":"2026012811274756100_R3","first-page":"42","article-title":"Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum.","volume-title":"Malar. J.","year":"2008"},{"key":"2026012811274756100_R4","first-page":"93","article-title":"Epidemiology and burden of malaria in pregnancy.","volume-title":"Lancet Infect. Dis.","year":"2007"},{"key":"2026012811274756100_R5","first-page":"2839","article-title":"Murine malaria infection induces fetal loss associated with accumulation of Plasmodium chabaudi AS-infected erythrocytes in the placenta.","volume-title":"Infect. Immun.","year":"2006"},{"key":"2026012811274756100_R6","first-page":"4850","article-title":"Pathology of Plasmodium chabaudi chabaudi infection and mortality in interleukin-10-deficient mice are ameliorated by anti-tumor necrosis factor alpha and exacerbated by anti-transforming growth factor \u03b2 antibodies.","volume-title":"Infect. Immun.","year":"2003"},{"key":"2026012811274756100_R7","first-page":"4399","article-title":"Central role of endogenous gamma interferon in protective immunity against blood-stage Plasmodium chabaudi AS infection.","volume-title":"Infect. Immun.","year":"2000"},{"key":"2026012811274756100_R8","first-page":"163","article-title":"Interferon-\u03b3: an overview of signals, mechanisms and functions.","volume-title":"J. Leukocyte Biol.","year":"2004"},{"key":"2026012811274756100_R9","first-page":"81S","article-title":"TNF in pathophysiology: biosynthetic regulation.","volume-title":"J. Invest. Dermatol.","year":"1990"},{"key":"2026012811274756100_R10","first-page":"44","article-title":"In vivo regulation of nitric oxide production by tumor necrosis factor alpha and gamma interferon, but not by interleukin-4, during blood stage malaria in mice.","volume-title":"Infect. Immun.","year":"1996"},{"key":"2026012811274756100_R11","first-page":"220","article-title":"Plasmodium chabaudi chabaudi (AS): inflammatory cytokines and pathology in an erythrocytic-stage infection in mice.","volume-title":"Exp. Parasitol.","year":"1998"},{"key":"2026012811274756100_R12","first-page":"1623","article-title":"Tumor necrosis factor \u03b1 in the pathogenesis of cerebral malaria.","volume-title":"Cell. Mol. Life Sci.","year":"2003"},{"key":"2026012811274756100_R13","first-page":"91","article-title":"Anti-TNF therapy inhibits fever in cerebral malaria.","volume-title":"Q. J. Med.","year":"1993"},{"key":"2026012811274756100_R14","first-page":"279","article-title":"A low interleukin-10 tumor necrosis factor-\u03b1 ratio is associated with malaria anemia in children residing in a holoendemic malaria region in western Kenya.","volume-title":"J. Infect. Dis.","year":"1999"},{"key":"2026012811274756100_R15","first-page":"267","article-title":"Placental tumor necrosis factor alpha but not gamma interferon is associated with placental malaria and low birth weight in Malawian women.","volume-title":"Infect. Immun.","year":"2003"},{"key":"2026012811274756100_R16","first-page":"1987","article-title":"Malaria and pregnancy: placental cytokine expression and its relationship to intrauterine growth retardation.","volume-title":"J. Infect. Dis.","year":"1999"},{"key":"2026012811274756100_R17","first-page":"259","article-title":"Interferon \u03b3 contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy.","volume-title":"J. Exp. Med.","year":"2000"},{"key":"2026012811274756100_R18","first-page":"554","article-title":"Tumor necrosis factors: pivotal components of pregnancy?.","volume-title":"Biol. Reprod.","year":"1996"},{"key":"2026012811274756100_R19","first-page":"2219","article-title":"Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions.","volume-title":"Hum. Reprod.","year":"2001"},{"key":"2026012811274756100_R20","first-page":"74","article-title":"Stress-triggered abortion: inhibition of protective suppression and promotion of tumor necrosis factor-\u03b1 (TNF-\u03b1) release as a mechanism triggering resorptions in mice.","volume-title":"Am. J. Reprod. Immunol.","year":"1995"},{"key":"2026012811274756100_R21","first-page":"879","article-title":"Tumor necrosis factor-\u03b1 and oxidant status are essential participating factors in unexplained recurrent spontaneous abortions.","volume-title":"Clin. Chem. Lab. Med.","year":"2007"},{"key":"2026012811274756100_R22","first-page":"417","article-title":"The interactions between inflammation and coagulation.","volume-title":"Br. J. Haematol.","year":"2005"},{"key":"2026012811274756100_R23","first-page":"4101","article-title":"Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury.","volume-title":"Blood","year":"2009"},{"key":"2026012811274756100_R24","first-page":"26419","article-title":"Mechanism of the tumor necrosis factor \u03b1-mediated induction of endothelial tissue factor.","volume-title":"J. Biol. Chem.","year":"1995"},{"key":"2026012811274756100_R25","first-page":"436","article-title":"Expression of tissue factor, the clotting initiator, on macrophages in Plasmodium falciparum-infected placentas.","volume-title":"J. Infect. Dis.","year":"2002"},{"key":"2026012811274756100_R26","first-page":"81","article-title":"Blood coagulation, inflammation, and malaria.","volume-title":"Microcirculation","year":"2008"},{"key":"2026012811274756100_R27","first-page":"59","article-title":"Coagulation disorders in experimentally induced acute mouse malaria.","volume-title":"Acta Trop.","year":"1991"},{"key":"2026012811274756100_R28","first-page":"2207","article-title":"Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes: evidence for an autocrine role of tumor necrosis factor and IL-1 \u03b2 in mediating the production of IL-8 triggered by lipopolysaccharide.","volume-title":"J. Exp. Med.","year":"1993"},{"key":"2026012811274756100_R29","first-page":"343","article-title":"Coagulation and fibrinolysis related cytokine imbalance in preeclampsia: the role of placental trophoblasts.","volume-title":"J. Perinat. Med.","year":"2009"},{"key":"2026012811274756100_R30","first-page":"105","article-title":"Malaria in pregnancy: pathogenesis and immunity.","volume-title":"Lancet Infect. Dis.","year":"2007"},{"key":"2026012811274756100_R31","first-page":"359","article-title":"The sick placenta: the role of malaria.","volume-title":"Placenta","year":"2004"},{"key":"2026012811274756100_R32","first-page":"398","article-title":"The effects of Plasmodium falciparum and P. vivax infections on placental histopathology in an area of low malaria transmission.","volume-title":"Am. J. Trop. Med. Hyg.","year":"2004"},{"key":"2026012811274756100_R33","first-page":"5","article-title":"Clinical features of malaria in pregnancy.","volume-title":"Malaria and Ankylomiasis in the Pregnant Woman","year":"1937"},{"key":"2026012811274756100_R34","first-page":"375","article-title":"The course of Plasmodium chabaudi chabaudi infections in interferon-\u03b3 receptor deficient mice.","volume-title":"Parasite Immunol.","year":"1997"},{"key":"2026012811274756100_R35","first-page":"3671","article-title":"Role of gamma interferon during infection with Plasmodium chabaudi chabaudi.","volume-title":"Infect. Immun.","year":"1990"},{"key":"2026012811274756100_R36","first-page":"971","article-title":"Absolute levels and ratios of proinflammatory and anti-inflammatory cytokine production in vitro predict clinical immunity to Plasmodium falciparum malaria.","volume-title":"J. Infect. Dis.","year":"2002"},{"key":"2026012811274756100_R37","first-page":"1218","article-title":"Immunity to placental malaria. I. Elevated production of interferon-\u03b3 by placental blood mononuclear cells is associated with protection in an area with high transmission of malaria.","volume-title":"J. Infect. Dis.","year":"1999"},{"key":"2026012811274756100_R38","first-page":"819","article-title":"Cytotoxicity of tumour necrosis factor-\u03b1 and \u03b3-interferon against primary human placental trophoblasts.","volume-title":"Placenta","year":"1994"},{"key":"2026012811274756100_R39","first-page":"430","article-title":"Plasmodium falciparum pigment induces monocytes to release high levels of tumor necrosis factor-\u03b1 and interleukin-1\u03b2.","volume-title":"Am. J. Trop. Med. Hyg.","year":"1994"},{"key":"2026012811274756100_R40","first-page":"1193","article-title":"Macrophage activation during Plasmodium chabaudi AS infection in resistant C57BL\/6 and susceptible A\/J mice.","volume-title":"Infect. Immun.","year":"1992"},{"key":"2026012811274756100_R41","first-page":"535","article-title":"A Th1-associated increase in tumor necrosis factor alpha expression in the spleen correlates with resistance to blood-stage malaria in mice.","volume-title":"Infect. Immun.","year":"1996"},{"key":"2026012811274756100_R42","first-page":"246","article-title":"Tumor necrosis factor in malaria-induced abortion.","volume-title":"Am. J. Trop. Med. Hyg.","year":"1988"},{"key":"2026012811274756100_R43","first-page":"262","article-title":"Soluble receptors neutralizing TNF-\u03b1 and IL-1 block stress-triggered murine abortion.","volume-title":"Am. J. Reprod. Immunol.","year":"1997"},{"key":"2026012811274756100_R44","first-page":"219","article-title":"Pregnancy: success and failure within the Th1\/Th2\/Th3 paradigm.","volume-title":"Semin. Immunol.","year":"2001"},{"key":"2026012811274756100_R45","first-page":"1015","article-title":"Role of tissue factor in hemostasis, thrombosis, and vascular development.","volume-title":"Arterioscler. Thromb. Vasc. Biol.","year":"2004"},{"key":"2026012811274756100_R46","first-page":"331","article-title":"The thrombomodulin-protein C system is essential for the maintenance of pregnancy.","volume-title":"Nat. Med.","year":"2003"},{"key":"2026012811274756100_R47","first-page":"258","article-title":"Does activation of the blood coagulation cascade have a role in malaria pathogenesis?.","volume-title":"Trends Parasitol.","year":"2008"},{"key":"2026012811274756100_R48","first-page":"776","article-title":"Tissue factor and tissue factor pathway inhibitor levels in trophoblast cells: implications for placental hemostasis.","volume-title":"Thromb. Haemostasis","year":"2004"},{"key":"2026012811274756100_R49","first-page":"17","article-title":"The dynamics of thrombin formation.","volume-title":"Arterioscler. Thromb. Vasc. Biol.","year":"2003"},{"key":"2026012811274756100_R50","first-page":"630","article-title":"Characterization of a model of malaria in the pregnant host: Plasmodium berghei in the white rat.","volume-title":"Am. J. Trop. Med. Hyg.","year":"1989"},{"key":"2026012811274756100_R51","first-page":"384","article-title":"Plasmodium falciparum-infected red blood cells selected for binding to cultured syncytiotrophoblast bind to chondroitin sulfate A and induce tyrosine phosphorylation in the syncytiotrophoblast.","volume-title":"Placenta","year":"2006"},{"key":"2026012811274756100_R52","first-page":"1740","article-title":"The impact of placental malaria on gestational age and birth weight.","volume-title":"J. Infect. Dis.","year":"2000"},{"key":"2026012811274756100_R53"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/8\/5342\/62694426\/9792.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/183\/8\/5342\/62694426\/9792.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T16:31:04Z","timestamp":1769617864000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/183\/8\/5342\/8053693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2009,10,15]]},"published-print":{"date-parts":[[2009,10,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0901669","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,10]]},"published":{"date-parts":[[2009,10]]}}}