Platelets interact with endothelial and immune cells in the circulation, orchestrating a response to microbes, inflammatory stimuli and vessel damage. Through their TLRs (or inflammatory signals) platelets can change their surface expression and release their granule content thereby engaging different immune cells. Platelets form HAGs and initiate innate immune responses in the presence of TLR agonists and viruses such as EMCV, CVB, dengue, flu, HIV. Platelets can interact with DC through their P-selectin, activate them to become Ag-presenting through their CD154. By releasing α- or δ-granule content which leads to IgG (IgG1, IgG2, IgG3) production and control of T-cell function, platelets engage the adaptive immune response. Similarly, platelets are able to activate the endothelium, make it more permeable and mediate leukocyte trafficking to the inflamed endothelium. Proteins in bold represent changes of expression on the platelet surface. Continuous lines represent direct binding; dotted lines represent interaction through secretion. Abbreviations: HAG-heterotypic aggregates; Ag-antigen; 5-HT-serotonin; PF4-platelet factor 4; CMV- cytomegalovirus; EMCV-encephalomyocarditis virus; CVB-coxsackievirus B;