title: Host responses to Plasmodium yoelii hepatic stages: a paradigm in host-parasite interaction.
abstract: The liver stage of malaria, caused by the genus Plasmodium, is clinically silent, but immunologically significant. Ample evidence exists for an effective CD8(+) T cell response to this stage as well as the involvement of gammadeltaT cells and NK1.1(int) cells in immunized animal models. In contrast, there is little information concerning responses in a naive host. Here we report that several host gene expressions in the liver, spleen, and kidney of BALB/c mice are altered during the liver stage of Plasmodium yoelii infection. Really interesting new gene 3 (Ring3), semaphorin subclass 4 member G, glutamylcysteine synthetase, and p45 NF erythroid 2 were all up-regulated 24 h after infection with P. yoelii. Semaphorin subclass 4 member G expression was elevated in the kidney, whereas Ring3 was elevated in both spleen and kidney. The expression of TNF-alpha (TNF-alpha and IFN-gamma) were down-regulated in all three tissues tested except in infected spleen where IFN-gamma was elevated. P. yoelii-related host gene changes were compared with those in Toxoplasma gondii-infected livers. Ring3 expression increased 5-fold over control values, whereas expression of the other transcripts remained unchanged. TNF-alpha and IFN-gamma expressions were increased in the Toxoplasma-infected livers. The uniform increase of Ring3 expression in both Plasmodium- and Toxoplasma-infected livers suggests an innate immune response against parasitic infections, whereas the other gene expression changes are consistent with Plasmodium parasite-specific responses. Taken together, these changes suggest the immune responses to P. yoelii infection are both parasite and organ specific.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland, School of Medicine, Baltimore, MD 21201, USA. laua@ucla.edu
authors.forename: A O
authors.initials: AO
authors.lastname: Lau
authors.forename: J B
authors.initials: JB
authors.lastname: Sacci
authors.forename: A F
authors.initials: AF
authors.lastname: Azad
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006790:Host-Parasite Interactions; D008099:Liver / Q000276:immunology* / Q000469:parasitology*; D008288:Malaria / Q000201:enzymology / Q000276:immunology* / Q000469:parasitology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D050984:NF-E2 Transcription Factor, p45 Subunit; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010967:Plasmodium yoelii / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D039961:Semaphorins; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D000092468:Bromodomain Containing Proteins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D008565:Membrane Proteins; D050984:NF-E2 Transcription Factor, p45 Subunit; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D039961:Semaphorins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C490844:Brd2 protein, mouse; D000092468:Bromodomain Containing Proteins; C405064:Sema4g protein, mouse