Brucellosis is a worldwide zoonosis that affects domestic animals and humans. The pathogenesis exhibited by this disease differs remarkably between humans and animals (35, 43). In domestic animals, brucellosis is mainly an abortive disease that results from a long-lasting often-unapparent infection. On the other hand, human brucellosis, also named Malta fever, is a complex disease that begins with a systemic infection that can be followed either by localized infection or chronic disease (15,29,43). Murine models are commonly used to study Brucella infection. Many strains of mice are sensitive to Brucella spp. but develop a disease quite different from that observed in domestic animals or in humans. Infection with Brucella does not modify pregnancy in mice, and acute infection results in a long-lasting presence of bacteria in the spleen and liver, predominantly. In humans, chronic infection is characterized by a specific bacterial localization within the body (spleen, liver, heart, bones, and brain) and a deleterious effect of the bacteria on these organs (43). The difference in pathogeny results most likely from differences in the immune responses in humans, domestic animals, and animal models (14). Some important differences between the immune responses of mice and humans have been reported. Brucella suis inhibits macrophage tumor necrosis factor alpha (TNF-␣) production in humans but not in mice (7,8) and this property is due to the outer membrane protein Omp25 (23). Furthermore, humans possess a specific type of circulating lymphocytes, called T␥9␦2, which is absent in mice. These lymphocytes proliferate importantly in human blood after Brucella infection (2) and impair intramacrophagic multiplication (36, 37).The mouse immune response has been widely studied (1, 19) although the reasons for the persistence of Brucella are not understood (22). The immune response in mammals can be divided into innate and adaptive immunity. Although the adaptive immunity is the most efficient response to eliminate infectious agents, it is widely accepted that innate response determines the behavior of specific response particularly in defining Th1 versus Th2 polarized response. Thus, the innate response is very important for the evolution of the infection. The importance of the Th1 cytokine gamma interferon (IFN-␥) in controlling infection in mice has been emphasized (1, 33). Among the cells involved in IFN-␥ production, NK cells play a particular role; they are the most important IFN-␥ producers in the beginning of infection. However, it has been clearly demonstrated that NK cells do not play a major role in the early control of Brucella abortus infection in mice (18). On the other hand, it was formally established that in the acute phase of the illness, the activity of the NK cells is impaired in humans developing brucellosis (40). Moreover, human NK cells were recently shown to mediate the intracellular killing of Mycobacterium tuberculosis (4). Therefore, in order to better understand the role of NK cells in bacterial deve...