NK cells express a repertoire Vismodegib mouse of activating and inhibitory receptors on their surface, which recognize aberrant cells. Some of these receptors are constitutively expressed by almost all NK cells, whereas the expression of others is tightly regulated by environmental stimuli. NK-cell activation is controlled by the balance between activating and inhibitory signals from target cells. NKp30, NKp44, and NKp46 belong to the natural cytotoxicity receptor family, NKG2D is a c-type

lectin molecule and all these receptors are involved in NK-cell-mediated cytolysis [12]. The inhibitory receptors include killer cell Ig-like receptors (KIR), such as KIR2DL2/3 (CD158b), which bind to class I MHC molecules [13]. MHC-restricted recognition enables NK cells to discriminate between healthy and transformed cells. It is now widely recognized that NK cells are important mediators during viral infections, particularly in terms of their role in mediating the clearance of infected cells [14]. Moreover, NK cells interact with DCs and MΦs, thereby potentiating immune mechanisms. These interactions promote cell activation, cytokine production, NK-cell proliferation and cytotoxicity, and DC and MΦ maturation [15]. During viral infections, DCs

and MΦs can increase IFN-γ production by NK cells, leading to the induction of a Th1-polarized T-cell response and the control of viral replication [16]. NK cells have also been check details shown to mediate the cytolysis of click here DCs infected with Ebola and Marburg viruses [17]. The role of NK cells in LASV infection remains unknown. We have previously shown that the LASV infection of NHPs leads to transient NK-cell depletion [18]. Given the important role of NK cells, knowledge of their contribution during infections would improve our understanding of the immune responses induced by LASV and MOPV. NHPs are the only relevant model for studies of the immunological mechanisms occurring during LF, but their use is limited due to BSL4 restrictions. Thus, we used an in vitro model of human NK cell and APC coculture

to study NK-cell activation in response to LASV and MOPV alone, or after stimulation with infected DCs and MΦs. This approach provides insight into the immune mechanisms operating during LF and clarifies the importance of NK/APC interactions in the initiation of immune responses. We investigated the potential of LASV and MOPV to infect NK cells. After immunofluorescence staining, no infected NK cells were observed and no infectious viral particles were detected in the super-natants (data not shown). Thus, LASV and MOPV were unable to infect NK cells. NK cells are known to express functional TLR3, TLR7, and TLR8 and are important sensors during infections, recognizing virus-derived RNAs [11]. We investigated the activation of NK cells in the presence of LASV or MOPV by flow cytometry.