Platelet CD154 contributes to the host defense against infections. Infection triggers inflammation and coagulation. The interaction with pathogens, pathogen-derived molecules such as lipopolysaccharide (LPS), inflammation and coagulation concur to activate platelets, leading to CD154 display at the platelet membrane and the release of soluble CD154 (sCD154). Multiple inputs amplify the platelet activation scenario, including soluble and cellular effectors of the inflammatory network. Platelet CD154 targets several immune response effectors, including contribution to the chemotactic recruitment (dotted semicircles symbolize chemotaxis) of leukocytes to sites of infection, e.g. through the induction of adhesion molecules on EC (CD62e, CD54, CD106) and activation/upregulation of integrins such as αMβ2 on neutrophils [158,200]. CD40 triggering is a major inducer of pathogen-killing mechanisms by phagocytic cells. These responses are amplified by inflammatory mediators generated upon CD40 ligation; this schematic representation does not represent all interfaces that are directly or indirectly regulated by platelet CD154. Platelet CD154 influences the adaptative immune response, through several mechanisms, including the activation/maturation of antigen presenting cells (see text for details). Magenta arrows depict interaction with CD40. Abbreviations: PAMPs, pathogen-associated molecular patterns; PRR, pathogen recognition receptors; TLR, Toll-like receptors.