Septicemia and Shock: Pathogenesis and Novel Therapeutic Strategies
(2003, NS 124)
Anna Norrby-Teglund, Staffan Normark, Ragnar Norrby, Malak Kotb, Thierry Calandra, Terje Espevik
May 15 - 17
Nobel Forum, Karolinska Institutet, Stockholm, Sweden
Proceedings: Scandinavian Journal of Infectious Diseases, Vol. 35, No. 9, 2003, Stockholm.

 

Bacterial Protein Toxins and Inflammation
Tomas Söderblom, Camilla Oxhamre, Elisabeth Torstensson, Agneta Richter-Dahlfors
Microbiology and Tumor biology Centre, Karolinska Institutet, S-171 77 Stockholm, Sweden

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. We recently discovered that the bacterial protein toxin a-haemolysin (HlyA), secreted by uropathogenic E. coli, induces constant, low-frequency Ca2⁺ oscillations in renal epithelial cells. Ca2⁺ oscillation occurs at a characteristic periodicity of 12 min, and was found to affect gene expression in target epithelial cells. Specifically, the pro-inflammatory cytokine IL-6 and chemokine IL-8 were induced by HlyA-induced Ca2⁺ oscillations. A few additional bacterial protein toxins have today 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-tunes gene expression in target epithelial cells.