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Bacterial Protein Toxins and Inflammation

Although human mucosal linings are continuously exposed to microbes, the microbes rarely induce disease. This is because mucosal surfaces are protected by a first line of defence termed the innate immunity system. Inflammatory processes are activated as a consequence of a complex interplay between microbes and host target cells. Although inflammation is essential for clearing out infectious agents, it can also be harmful to the host and is therefore subjected to tight control at multiple levels. It was recently discovered that the bacterial protein toxin α-haemolysin (HlyA), secreted by uropathogenic Escherichia coli, induces constant, low-frequency Ca2+ oscillations in renal epithelial cells. Ca2+ oscillation occurs at a characteristic periodicity of 12 min, and affects gene expression in target epithelial cells. Specifically, the proinflammatory cytokine interleukin-6 (IL-6) and chemokine IL-8 were induced by HlyA-induced Ca2+ oscillations. A few additional bacterial protein toxins have been reported to induce Ca2+ oscillations in target epithelial cells, although their effects are poorly understood. However, the pioneering work on HlyA demonstrates a novel feature of bacterial protein toxins on host target cells: as inducers of second messenger responses which fine-tune gene expression in target epithelial cells.