title: Gene profiling analysis reveals the contribution of CD24 and P2Y6R to the susceptibility of young rats to Plasmodium berghei infection.
abstract: Our previous studies have shown that Plasmodium berghei infection induces distinct clinical, parasitological and immunological states in young susceptible rats versus adult resistant rats. This susceptibility was mainly found to be related to inadequate cellular responses. In this study we first identified the altered genes in young susceptible rats. Unexpectedly, transcriptome analysis did not reveal any alteration of effector cytokines or their receptors. At day 13 p.i., six transcripts corresponding to faim3, mesothelin, gas3 (PMP22), gas7, CD24 and P2Y6R were significantly decreased in young infected rats when compared with adult infected rats. Because CD24 and P2Y6R participate in cellular immune responses, we next evaluated their role in the course of infection. Adoptive transfer experiments showed a transient but robust participation of CD24+ cells in the control of parasitaemia. The role of P2Y6R was investigated via its specific ability to be activated by Uridine di-Phosphate (UDP). Young rats treated with UDP partially restored the expression of P2Y6R, controlled parasitaemia and survived thereafter. In conclusion, this study contributes to the discovery of novel biomarkers in young susceptible rats and suggests that the decrease in their expression could be among the reasons for the development of severe pathology in malaria.
authors.affiliation: Center for Infection and Immunity of Lille, Institut Pasteur de Lille, INSERM U1019, CNRS UMR8204, University Lille Nord de France, IFR 142, 1 rue du Professeur A. Calmette, 59019 Lille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Pierrot
authors.forename: Aurore Acroute
authors.initials: AA
authors.lastname: dit Vampouille
authors.forename: Audrey
authors.initials: A
authors.lastname: Vandomme
authors.forename: Sophia
authors.initials: S
authors.lastname: Lafitte
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Pierce
authors.forename: David
authors.initials: D
authors.lastname: Hot
authors.forename: Jamal
authors.initials: J
authors.lastname: Khalife
mesh_terms: D000367:Age Factors; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D051927:CD24 Antigen / Q000235:genetics* / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D007111:Immunity, Cellular; D008288:Malaria / Q000235:genetics / Q000276:immunology*; D046228:Microarray Analysis; D010962:Plasmodium berghei / Q000276:immunology*; D016133:Polymerase Chain Reaction; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000235:genetics* / Q000276:immunology; D014530:Uridine Diphosphate / Q000494:pharmacology
chemical_list: D000954:Antigens, Surface; D051927:CD24 Antigen; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6; D014530:Uridine Diphosphate