Within one hour of exposure of whole blood to a concentration of LPS that has threshold effect on cytokine production in vivo, platelets become positive for leukocyte antigen. Platelet-leukocyte interactions require TLR4 signaling as the dual antigen positivity of platelets was observed in blood derived from wild type but not dTLR4 mice. Furthermore, peptide inhibitors of TLR4 signaling molecules blocked the interaction. These events occur within 1 hour after the initial exposure to LPS. In addition, effects of LPS stimulation are sustained at least up to 7 days past the initial LPS exposure, as leukocytes express platelet antigen at this time point. Collectively, these results identify an acute and rapid signaling mechanism by which sentinel-grade acute infection through TLR4 alters blood hemostasis and sustained leukocyte activation which may contribute to progression of cardiovascular diseases.  NKG2D contributes to efficient clearance of picornavirus from the acutely infected murine brain Activated murine cytotoxic T cells express the NKG2D natural cytotoxicity receptor. This receptor recognizes MHC class I-like molecules expressed on the surface of infected cells and serves to augment T cell-mediated cytotoxicity. The role of NKG2D-mediated augmentation in the clearance of central nervous system viral infections has not been explored. Using the Theiler's murine encephalomyelitis virus model we found that NKG2D-positive CD8+ cytotoxic T cells enter the brain, that NKG2D ligands are expressed in the brain during acute infection, and that interruption of NKG2D ligand recognition via treatment with a function blocking antibody attenuates the efficacy of viral clearance from the central nervous system. NKG2D is a natural cytotoxicity receptor expressed on natural killer cells (NKCs) and on activated CTLs in mice (Eagle and Trowsdale, 2007) . This receptor recognizes stress-and infection-regulated MHC class I-like molecules such as Rae1, Mult1, and H60 expressed on the surface of murine cells (Raulet, 2003) . While NKG2D is a direct mediator of cytotoxicity for NKCs, it serves as a co-stimulatory receptor for CTLs and augments cytotoxicity downstream from T cell receptor recognition of peptides presented on MHC class I (Markiewicz et al, 2005) . Because the mechanisms that direct CTL-mediated clearance of infected neural cells are unclear, we asked whether NKG2D-positive immune effectors are present in the CNS during acute TMEV infection, whether NKG2D ligands are expressed in the brain following infection, and whether interruption of NKG2D-mediated co-stimulation of CTLs alters viral clearance from the CNS.