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.