title: Analysis of innate defences against Plasmodium falciparum in immunodeficient mice.
abstract: BACKGROUND
  Mice with genetic deficiencies in adaptive immunity are used for the grafting of human cells or pathogens, to study human diseases, however, the innate immune responses to xenografts in these mice has received little attention. Using the NOD/SCID Plasmodium falciparum mouse model an analysis of innate defences responsible for the substantial control of P. falciparum which remains in such mice, was performed.
  
  
  METHODS
  NOD/SCID mice undergoing an immunomodulatory protocol that includes, clodronate-loaded liposomes to deplete macrophages and an anti-polymorphonuclear leukocytes antibody, were grafted with human red blood cells and P. falciparum. The systematic and kinetic analysis of the remaining innate immune responses included the number and phenotype of peripheral blood leukocytes as well as inflammatory cytokines/chemokines released in periphery. The innate responses towards the murine parasite Plasmodium yoelii were used as a control.
  
  
  RESULTS
  Results show that 1) P. falciparum induces a strong inflammation characterized by an increase in circulating leukocytes and the release of inflammatory cytokines; 2) in contrast, the rodent parasite P. yoelii, induces a far more moderate inflammation; 3) human red blood cells and the anti-inflammatory agents employed induce low-grade inflammation; and 4) macrophages seem to bear the most critical function in controlling P. falciparum survival in those mice, whereas polymorphonuclear and NK cells have only a minor role.
  
  
  CONCLUSIONS
  Despite the use of an immunomodulatory treatment, immunodeficient NOD/SCID mice are still able to mount substantial innate responses that seem to be correlated with parasite clearance. Those results bring new insights on the ability of innate immunity from immunodeficient mice to control xenografts of cells of human origin and human pathogens.
authors.affiliation: Laboratoire de Parasitologie Bio-Médicale, Institut Pasteur, 28, rue du Dr Roux, 75015 Paris, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Arnold
authors.forename: Rajeev Kumar
authors.initials: RK
authors.lastname: Tyagi
authors.forename: Pedro
authors.initials: P
authors.lastname: Mejia
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pérignon
authors.forename: Pierre
authors.initials: P
authors.lastname: Druilhe
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D007962:Leukocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010641:Phenotype; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D010967:Plasmodium yoelii / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology
chemical_list: D016207:Cytokines