title: Plasmodium chabaudi AS induces pregnancy loss in association with systemic pro-inflammatory immune responses in A/J and C57BL/6 mice.
abstract: The molecular mechanisms that underlie poor birth outcomes in malaria during pregnancy remain poorly defined. To assess the role of host immune responses, mice known to respond differentially to Plasmodium chabaudi AS infection were studied. Following infection at day 0 of pregnancy, A/J mice developed significantly higher parasitemia than C57BL/6 (B6) mice and succumbed to infection. Both strains had evidence of parasite accumulation in the placenta at mid-gestation and aborted, with significantly higher embryo loss in infected A/J mice on day 9. While infection-induced systemic tumour necrosis factor (TNF) and interleukin (IL)-1β in the latter were significantly higher at day 11, day 10 IL-10 levels were higher in B6 mice. No differences in the levels of splenic lymphocyte subsets, neutrophils or monocytes between infected pregnant A/J and B6 mice were observed, with most cell types expanding in response to infection regardless of pregnancy. Antibody ablation of TNF exacerbated infection in A/J mice and did not ameliorate pregnancy outcome. Thus, malaria induces poor pregnancy outcome in both the mouse strains in the context of quantitatively different systemic inflammatory responses. Further evaluation of the roles of soluble and cellular immune components, particularly at the uteroplacental level, will be required to define the most critical pregnancy-compromising mechanisms.
authors.affiliation: Department of Infectious Diseases, Center for Tropical and Emerging Global Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sarr
authors.forename: G M
authors.initials: GM
authors.lastname: Smith
authors.forename: J S
authors.initials: JS
authors.lastname: Poovassery
authors.forename: T
authors.initials: T
authors.lastname: Nagy
authors.forename: J M
authors.initials: JM
authors.lastname: Moore
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000276:immunology; D008288:Malaria / Q000150:complications / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000469:parasitology; D010920:Placenta / Q000469:parasitology; D016788:Plasmodium chabaudi / Q000472:pathogenicity*; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology* / Q000469:parasitology
chemical_list: D016207:Cytokines