Altogether, this suggests Selleckchem OSI 906 that other mechanisms may have intervened. The expression or upregulation of various NKG2D ligands is tightly regulated in cells by stress, infections and transformation mechanisms. There is ample evidence of pathogens driving the diversity of NKG2D ligands. Numerous studies demonstrated

that viral infections increase the expression of NKG2D ligands but also that some viruses deploy evasive maneuvers to prevent expression of NKG2D ligands on the cell surface. The protein UL16 of human CMV binds to ULBP1, ULBP2, ULBP6 and MICB and retains these ligands intracellularly 28. Other intracellular mechanisms or signaling pathways induced by the presence of microorganisms can also influence NKG2D ligand expression. GSI-IX datasheet Notably, TLR signaling results in NKG2D ligand transcription. TLR4 engagement by LPS has been reported to upregulate cell-surface ULBP1 and MICA/B on human myeloid DCs and the expression of ULBP2 was induced by PolyI:C treatment 42. Moreover, various data have been reported in the infection with Mycobacterium tuberculosis. While the infection of DCs with a high MOI (2000) of this bacterium upregulates MICA surface expression 43, the infection of monocytes or macrophages with a low MOI (20) induces only the upregulation of ULBP1 expression 44. Thus, NKG2D ligand expression can be different from one infection to another, from one cell population

to another and their impact on the anti-infectious activity of Vγ9Vδ2 T cells could also vary. In conclusion, this study provides evidence that NKG2D can fine-tune the anti-infectious responses of Vγ9Vδ2 T cells against intracellular bacterium, through its interaction with its ligands. In addition,

it suggests that NKG2D could also be involved in the anti-infectious activity of Vγ9Vδ2 T cells against all microorganisms that have the ability to positively modulate NKG2D ligand expression. In a more general way, this study showed that T cells that do not utilize classical coreceptors, Interleukin-3 receptor such as CD4 and CD8, take advantage of other stimulatory molecules for a more efficient activation as well as for delivery of their effector functions, in this case a bactericidal one. Soluble ULBP1-LZ, ULBP2-LZ, UL16-LZ fusion proteins, M585 and M580 mAbs to human NKG2D and M15 anti-LZ mAb were a generous gift from AMGEN (Seattle, USA). HMB-PP was generously provided by J. L. Montero (Montpellier, France). Anti-ULBP1, ULBP2, ULBP3 and MICA/B mAbs were purchased unconjugated or as FITC- or PE conjugates from R&D Systems (Minneapolis, MN, USA). Anti-ULBP4 was purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Anti-mouse and isotypically matched control mouse Abs (conjugated or not) were all purchased from BD Biosciences (San Jose, CA, USA). Control or NKG2D siRNA were purchased from Dharmacon (Lafayette, CO, USA).