title: Blood-stage malaria of Plasmodium chabaudi induces differential Tlr expression in the liver of susceptible and vaccination-protected Balb/c mice.
abstract: Protective vaccination induces self-healing of otherwise lethal blood-stage infections of Plasmodium chabaudi malaria. Here, we investigate mRNA expression patterns of all 12 members of the Toll-like receptor (Tlr) gene family in the liver, a major effector organ against blood-stage malaria, during lethal and vaccination-induced self-healing infections of P. chabaudi in female Balb/c mice. Gene expression microarrays reveal that all 12 Tlr genes are constitutively expressed, though at varying levels, and specifically respond to infection. Protective vaccination does not affect constitutive expression of any of the 12 Tlr genes but leads to differential expression (p < 0.05) of seven Tlrs (1, 2, 4, 7, 8, 12, and 13) in response to malaria. Quantitative PCR substantiates differential expression at p < 0.01. There is an increased expression of Tlr2 by approximately five-fold on day 1 post-infection (p.i.) and Tlr1 by approximately threefold on day 4 p.i.. At peak parasitemia on day 8 p.i., none of the 12 Tlrs display any differential expression. After peak parasitemia, towards the end of the crisis phase on day 11 p.i., expression of Tlrs 1, 4, and 12 is increased by approximately four-, two-, and three-fold, respectively, and that of Tlr7 is decreased by approximately two-fold. Collectively, our data suggest that though all 12 members of the Tlr gene family are specifically responsive to malaria in the liver, not only Tlr2 at the early stage of infection but also the Tlrs 1, 4, 7, and 12 towards the end of crisis phase are critical for vaccination-induced resolution and survival of otherwise lethal blood-stage malaria.
authors.affiliation: Department of Zoology, College of Science, King Saud University, PO Box 2455, Riyadh, 11451, Saudi Arabia. guraishi@yahoo.com.
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Quraishy
authors.affiliation: Department of Zoology, College of Science, King Saud University, PO Box 2455, Riyadh, 11451, Saudi Arabia.|Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Dkhil
authors.affiliation: Department of Zoology, College of Science, King Saud University, PO Box 2455, Riyadh, 11451, Saudi Arabia.
authors.forename: Suliman
authors.initials: S
authors.lastname: Alomar
authors.affiliation: Department of Zoology, College of Science, King Saud University, PO Box 2455, Riyadh, 11451, Saudi Arabia.|Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Abdel Azeem S
authors.initials: AA
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
authors.affiliation: Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain.|IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Araúzo-Bravo
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D008099:Liver / Q000276:immunology / Q000378:metabolism*; D008288:Malaria / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D018512:Parasitemia; D016788:Plasmodium chabaudi; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D014611:Vaccination
chemical_list: D017780:Malaria Vaccines; D051193:Toll-Like Receptors
keywords: Blood-stage malaria; Liver; Plasmodium chabaudi; Protective vaccination; Toll-like receptors; mRNA expression
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