The activation of NK cells observed in response to LASV- and MOPV-infected MΦs is particularly interesting in that it is almost as robust as for positive controls, regarding the expression of NKp30 for instance, but nevertheless presents a different phenotype. We show here that LASV and MOPV do not infect NK cells. This result was expected and consistent

with previous studies showing that α-dystroglycan, the LASV and MOPV entry receptor, is expressed preferentially Small Molecule Compound Library on DCs and poorly on lymphocytes and that lymphocytic choriomeningitis virus, the prototypic Arenavirus that is closely related to LASV and MOPV, can infect only a few types of lymphocyte. Moreover, after direct contact with the viruses, NK cells were not activated and displayed no change in their effector functions. A slight downregulation of NKp30 expression and an increase in the expression of CXCR3 on the cell surface was even

observed in the presence of LASV or MOPV. Interestingly, TLR7 stimulation induced NKp30 downregulation as well. These results suggested that NK cells can detect both viruses, possibly through TLR7 stimulation requiring further investigation. NK cells display a rapid decrease in surface CXCR3 when cocultured learn more with LASV- or MOPV-infected MΦs. However, the significance of this downregulation is unclear. It is unlikely to be accounted for by the modulation of CXCR3 mRNA synthesis, as analysis of the mRNAs revealed no change during LASV or MOPV infection (data not shown). Aspartate CXCR3 is the receptor for the inflammatory chemokines CXCL9, 10, and 11. These chemokines, initially described as attracting activated T lymphocytes, are secreted in large amounts during the infection of MΦs with LASV and MOPV in vitro (Pannetier et al., manuscript in preparation). Moreover, the transcripts for CXCL10 and CXCL11 are found in PBMCs and lymph nodes from infected Cynomolgus monkeys [18]

and we show here that CXCL11 is detected in LASV- and MOPV-infected NK/MΦ cocultures. CXC chemokines, such as CXCL11, have been reported to induce the rapid desensitization and internalization of their receptor, CXCR3 [20]. Thus, the downregulation of surface CXCR3 expression could partly be accounted for by receptor internalization. This hypothesis is consistent with our observations, showing that CXCR3 surface expression is also downregulated when cell contact is prevented, implying that soluble factors are involved. Moreover, it is also consistent with our results with neutralizing Ab directed against CXC chemokines that abolish or reduce the downregulation of CXCR3 at the surface on NK cells in the presence of LASV- or MOPV-infected MΦs respectively.