Analysis of innate defences against Plasmodium falciparum in immunodeficient mice.
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.
Arnold
Ludovic
L
Laboratoire de Parasitologie Bio-Médicale, Institut Pasteur, 28, rue du Dr Roux, 75015 Paris, France.
Tyagi
Rajeev Kumar
RK
Mejia
Pedro
P
Van Rooijen
Nico
N
Pérignon
Jean-Louis
JL
Druilhe
Pierre
P
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
D016207:Cytokines