Natural killer cell and macrophage cooperation in MyD88-dependent innate responses to Plasmodium falciparum.
IFN-gamma secretion by natural killer (NK) cells is pivotal to several tumor and viral immune responses, during which NK and dendritic cells cooperation is required. We show here that macrophages are mandatory for NK cell IFN-gamma secretion in response to erythrocytes infected with Plasmodium falciparum (Pf), a causative agent of human malaria. In addition, direct sensing of Pf infection by NK cells induces their production of the proinflammatory chemokine CXCL8, without triggering their granule-mediated cytolytic programs. Despite their reported role in Pf recognition, Toll-like receptor (TLR) 2, TLR9, and TLR11 are individually dispensable for NK cell activation induced by Pf-infected erythrocytes. However, IL-18R expression on NK cells, IL-18 production by macrophages, and MyD88 on both cell types are essential components of this previously undescribed pathway of NK cell activation in response to a parasite infection.
Baratin
Myriam
M
Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université delaMéditerranée, 13288 Marseille, France.
Roetynck
Sophie
S
Lépolard
Catherine
C
Falk
Christine
C
Sawadogo
Serge
S
Uematsu
Satoshi
S
Akira
Shizuo
S
Ryffel
Bernhard
B
Tiraby
Jean-Gérard
JG
Alexopoulou
Lena
L
Kirschning
Carsten J
CJ
Gysin
Jürg
J
Vivier
Eric
E
Ugolini
Sophie
S
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000818:Animals; D019743:Chemokines, CXC / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88; D010963:Plasmodium falciparum / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D019743:Chemokines, CXC; D020382:Interleukin-18; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; D007371:Interferon-gamma