Contribution of the Ly49E natural killer receptor in the immune response to Plasmodium berghei infection and control of hepatic parasite development.
Natural killer (NK) cells have different roles in the host response against Plasmodium-induced malaria depending on the stage of infection. Liver NK cells have a protective role during the initial hepatic stage of infection by production of the TH1-type cytokines IFN-γ and TNF-α. In the subsequent erythrocytic stage of infection, NK cells also induce protection through Th1-type cytokines but, in addition, may also promote development of cerebral malaria via CXCR3-induction on CD8(+) T cells resulting in migration of these cells to the brain. We have recently shown that the regulatory Ly49E NK receptor is expressed on liver NK cells in particular. The main objective of this study was therefore to examine the role of Ly49E expression in the immune response upon Plasmodium berghei ANKA infection, for which we compared wild type (WT) to Ly49E knockout (KO) mice. We show that the parasitemia was higher at the early stage, i.e. at days 6-7 of Plasmodium berghei ANKA infection in Ly49E KO mice, which correlated with lower induction of CD69, IFN-γ and TNF-α in DX5(-) liver NK cells at day 5 post-infection. At later stages, these differences faded. There was also no difference in the kinetics and the percentage of cerebral malaria development and in lymphocyte CXCR3 expression in WT versus Ly49E KO mice. Collectively, we show that the immune response against Plasmodium berghei ANKA infection is not drastically affected in Ly49E KO mice. Although NK cells play a crucial role in Plasmodium infection and Ly49E is highly expressed on liver NK cells, the Ly49E NK receptor only has a temporarily role in the immune control of this parasite.
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Jessica
J
Filtjens
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Lander
L
Foquet
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Sylvie
S
Taveirne
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Els
E
Van Ammel
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Mandy
M
Vanhees
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Aline
A
Van Acker
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Tessa
T
Kerre
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Tom
T
Taghon
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Bart
B
Vandekerckhove
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Jean
J
Plum
Laboratory of Immunobiology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Philippe E
PE
Van den Steen
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Georges
G
Leclercq
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000469:parasitology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D008099:Liver / Q000276:immunology* / Q000469:parasitology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D010962:Plasmodium berghei / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007371:Interferon-gamma; D037181:Lectins, C-Type; D054367:Receptors, CXCR3; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens; C515188:Cxcr3 protein, mouse