Immune proteomics is an increasingly powerful tool for the investigation of the adaptive immune response to natural encounters between micro-organisms and their hosts. The versatile species Staphylococcus aureus serves to illustrate how these techniques can be employed to appreciate the complexity and diversity of the host-pathogen interactions in unprecedented detail and completeness. Such knowledge is important for the development of effective vaccines as well as informative diagnostic and novel therapeutic tools. From high-resolution immune proteome studies, general rules underlying the human adaptive immune response to S. aureus colonization and infection are beginning to emerge against a background of extreme diversity: S. aureus carriers develop immune memory for their colonizing strain, but even non-carriers are frequently exposed to S. aureus, resulting in specific antibodies. During bacterial invasion, immune-competent individuals rapidly mount an antibody response to a large panel of S. aureus antigens. However, every patient starts from a personal baseline antibody profile reflecting his or her history of encounters with S. aureus.
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