Association of malaria-induced murine pregnancy failure with robust peripheral and placental cytokine responses.
Malarial infection in nonimmune pregnant women is a major risk factor for pregnancy failure. The biological mechanisms that underlie malaria-associated fetal loss, however, are poorly understood. Plasmodium chabaudi AS infection during early pregnancy results in midgestational embryonic loss in naive C57BL/6 mice. To define the immunopathogenesis of this malaria-induced pregnancy compromise, cytokine production in plasma, spleen, and placenta cell culture supernatants during the first 11 days of infection and gestation was studied. In infected pregnant mice, systemic interleukin-1beta and both systemic and splenic gamma interferon levels were elevated relative to those in uninfected pregnant mice, and gamma interferon was also robustly produced within the placenta 1 to 2 days before malaria-induced fetal loss. Although circulating tumor necrosis factor production was not affected by pregnancy or infection, circulating soluble tumor necrosis factor receptor II was highest in infected pregnant mice, particularly those undergoing abortion, but decreased at the placental level preceding abortion. Systemic levels of interleukin-10 were also high in infected mice at this time point, but this cytokine was not detected at the placental level. Histological examination revealed that trophoblast giant cells of aborting mice phagocytosed infected red blood cells and hemozoin. Furthermore, in vitro-cultured trophoblast cells isolated from embryos on day 7 of gestation phagocytosed P. chabaudi AS-infected red blood cells and secreted tumor necrosis factor. These results suggest that systemic and placenta-level proinflammatory antimalarial immune responses, in the absence of adequate and sustained counterregulatory mechanisms, contribute to pregnancy loss in this model.
Poovassery
Jayakumar
J
Department of Infectious Diseases, Center for Tropical and Emerging Global Diseases, Paul Coverdell Center, Room 330, University of Georgia, 500 DW Brooks Dr., Athens, GA 30602, USA.
Moore
Julie M
JM
D000818:Animals; D016207:Cytokines / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000276:immunology*; D016788:Plasmodium chabaudi / Q000276:immunology; D011247:Pregnancy / Q000276:immunology*; D015597:Pregnancy Complications, Parasitic / Q000276:immunology*
D016207:Cytokines
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