The innate immune system is a highly effective and redundant system to remove and kill invading bacteria. In order to survive in the human host, bacteria have developed a strategy to escape the innate immune system. Bacteria produce a capsule, adapt to an intracellular lifestyle or secrete small proteins that specifically and with high affinity block effectors and recognition molecules in innate immunity. We identified a large array of innate immune evasion molecules in the last years in staphylococci. We discovered chemotaxis inhibitors and their targets; Complement inhibitors and their complex mechanism of action; opsonin-removers; rolling inhibitors, and many more. In the process we have gained insight in both bacterial pathogenisis and our immune system. It is now clear that this is just the tip of the iceberg.
Several toxins secreted by staphylococci have been reported to lyse red blood cells (hemolysins), white blood cells (leukocidins) or all mammalian cells (like the staphylococcal PSM). Some of these toxins (like the Panton Valentine Leukocidin or PVL) have been known for decades and are important in serious disease or disease states. The mechanism of action and the precise receptors were unknown. In a series of papers we now demonstrated that the most-if not all- staphylococcal toxins are in fact immune evasion molecules. Either by direct recognition of phagocyte specific receptors (as the C5aR) or by indirect mechanisms that involves intraphagosomal Quorum Sensing, all of these toxins specifically target and kill phagocytes. In this way Staphylococci subvert the human primary defense system and can cause disease. This will have major consequences for vaccine design in the future.