title: The impact of genetic susceptibility to systemic lupus erythematosus on placental malaria in mice.
abstract: Severe malaria, including cerebral malaria (CM) and placental malaria (PM), have been recognized to have many of the features of uncontrolled inflammation. We recently showed that in mice genetic susceptibility to the lethal inflammatory autoimmune disease, systemic lupus erythematosus (SLE), conferred resistance to CM. Protection appeared to be mediated by immune mechanisms that allowed SLE-prone mice, prior to the onset of overt SLE symptoms, to better control their inflammatory response to Plasmodium infection. Here we extend these findings to ask does SLE susceptibility have 1) a cost to reproductive fitness and/or 2) an effect on PM in mice? The rates of conception for WT and SLE susceptible (SLE(s)) mice were similar as were the number and viability of fetuses in pregnant WT and SLE(s) mice indicating that SLE susceptibility does not have a reproductive cost. We found that Plasmodium chabaudi AS (Pc) infection disrupted early stages of pregnancy before the placenta was completely formed resulting in massive decidual necrosis 8 days after conception. Pc-infected pregnant SLE(s) mice had significantly more fetuses (∼1.8 fold) but SLE did not significantly affect fetal viability in infected animals. This was despite the fact that Pc-infected pregnant SLE(s) mice had more severe symptoms of malaria as compared to Pc-infected pregnant WT mice. Thus, although SLE susceptibility was not protective in PM in mice it also did not have a negative impact on reproductive fitness.
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America. waisberg@gmail.com
authors.forename: Michael
authors.initials: M
authors.lastname: Waisberg
authors.forename: Christina K
authors.initials: CK
authors.lastname: Lin
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Mirna
authors.initials: M
authors.lastname: Pena
authors.forename: Marlene
authors.initials: M
authors.lastname: Orandle
authors.forename: Silvia
authors.initials: S
authors.lastname: Bolland
authors.forename: Susan K
authors.initials: SK
authors.lastname: Pierce
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004909:Erythrocyte Indices; D005260:Female; D020022:Genetic Predisposition to Disease; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D008288:Malaria / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D018512:Parasitemia / Q000235:genetics / Q000276:immunology; D010920:Placenta / Q000469:parasitology* / Q000473:pathology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic; D012098:Reproduction / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index