title: CD8+ T cells and IFN-γ mediate the time-dependent accumulation of infected red blood cells in deep organs during experimental cerebral malaria.
abstract: BACKGROUND
  Infection with Plasmodium berghei ANKA (PbA) in susceptible mice induces a syndrome called experimental cerebral malaria (ECM) with severe pathologies occurring in various mouse organs. Immune mediators such as T cells or cytokines have been implicated in the pathogenesis of ECM. Red blood cells infected with PbA parasites have been shown to accumulate in the brain and other tissues during infection. This accumulation is thought to be involved in PbA-induced pathologies, which mechanisms are poorly understood.
  
  
  RESULTS
  Using transgenic PbA parasites expressing the luciferase protein, we have assessed by real-time in vivo imaging the dynamic and temporal contribution of different immune factors in infected red blood cell (IRBC) accumulation and distribution in different organs during PbA infection. Using deficient mice or depleting antibodies, we observed that CD8(+) T cells and IFN-γ drive the rapid increase in total parasite biomass and accumulation of IRBC in the brain and in different organs 6-12 days post-infection, at a time when mice develop ECM. Other cells types like CD4(+) T cells, monocytes or neutrophils or cytokines such as IL-12 and TNF-α did not influence the early increase of total parasite biomass and IRBC accumulation in different organs.
  
  
  CONCLUSIONS
  CD8(+) T cells and IFN-γ are the major immune mediators controlling the time-dependent accumulation of P. berghei-infected red blood cells in tissues.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore, Singapore.
authors.forename: Carla
authors.initials: C
authors.lastname: Claser
authors.forename: Benoît
authors.initials: B
authors.lastname: Malleret
authors.forename: Sin Yee
authors.initials: SY
authors.lastname: Gun
authors.forename: Alicia Yoke Wei
authors.initials: AY
authors.lastname: Wong
authors.forename: Zi Wei
authors.initials: ZW
authors.lastname: Chang
authors.forename: Pearline
authors.initials: P
authors.lastname: Teo
authors.forename: Peter Chi Ee
authors.initials: PC
authors.lastname: See
authors.forename: Shanshan Wu
authors.initials: SW
authors.lastname: Howland
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
mesh_terms: D000818:Animals; D018533:Biomass; D001921:Brain / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D008212:Lymphocyte Depletion; D016779:Malaria, Cerebral / Q000276:immunology* / Q000469:parasitology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology; D009928:Organ Specificity / Q000276:immunology*; D010962:Plasmodium berghei / Q000502:physiology; D013997:Time Factors
chemical_list: D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D007371:Interferon-gamma