title: Differential miRNA Expression in the Liver of Balb/c Mice Protected by Vaccination during Crisis ofPlasmodium chabaudiBlood-Stage Malaria.
abstract: MicroRNAs are increasingly recognized as epigenetic regulators for outcome of diverse infectious diseases and vaccination efficacy, but little information referring to this exists for malaria. This study investigates possible effects of both protective vaccination andP. chabaudimalaria on the miRNome of the liver as an effector against blood-stage malaria using miRNA microarrays and quantitative PCR.Plasmodium chabaudiblood-stage malaria takes a lethal outcome in female Balb/c mice, but a self-healing course after immunization with a non-infectious blood-stage vaccine. The liver robustly expresses 71 miRNA species at varying levels, among which 65 miRNA species respond to malaria evidenced as steadily increasing or decreasing expressions reaching highest or lowest levels toward the end of the crisis phase on day 11p.i. in lethal malaria. Protective vaccination does not affect constitutive miRNA expression, but leads to significant (p< 0.05) changes in the expression of 41 miRNA species, however evidenced only during crisis. In vaccination-induced self-healing infections, 18 miRNA-species are up- and 14 miRNA-species are down-regulated by more than 50% during crisis in relation to non-vaccinated mice. Vaccination-induced self-healing and survival of otherwise lethal infections ofP. chabaudiactivate epigenetic miRNA-regulated remodeling processes in the liver manifesting themselves during crisis. Especially, liver regeneration is accelerated as suggested by upregulation of let-7a-5p, let-7b-5p, let-7c-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-26a, miR-122-5p, miR30a, miR27a, and mir-29a, whereas the up-regulated expression of miR-142-3p by more than 100% is compatible with the view of enhanced hepatic erythropoiesis, possibly at expense of megakaryopoiesis, during crisis ofP. chabaudiblood-stage malaria.
authors.affiliation: Department of Zoology, College of Science, King Saud UniversityRiyadh, Saudi Arabia; Department of Zoology and Entomology, Faculty of Science, Helwan UniversityCairo, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Dkhil
authors.affiliation: Department of Zoology, College of Science, King Saud University Riyadh, Saudi Arabia.
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Al-Quraishy
authors.affiliation: Department of Zoology, College of Science, King Saud UniversityRiyadh, Saudi Arabia; Department of Zoology, Faculty of Science, Beni-Suef UniversityBeni-Suef, Egypt.
authors.forename: Abdel-Azeem S
authors.initials: AS
authors.lastname: Abdel-Baki
authors.affiliation: Boehringer-Ingelheim Pharma Biberach, Germany.
authors.forename: Denis
authors.initials: D
authors.lastname: Delic
authors.affiliation: Department of Biology, Heinrich-Heine-University Duesseldorf, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Wunderlich
keywords: Plasmodium chabaudi; blood-stage malaria; liver; miRNA; protective vaccination