Book Description

Bacterial pathogenicity factors are functionally diverse. They may facilitate the adhesion and colonization of bacteria, influence the host immune response, assist spreading of the bacterium by e.g. evading recognition by immune cells, or allow bacteria to dwell within protected niches inside the eukaryotic cell. Exotoxins can be single polypeptides or heteromeric protein complexes that act on different parts of the cells. At the cell surface, they may insert into the membrane to cause damage; bind to receptors to initiate their uptake; or facilitate the interaction with other cell types. For example, bacterial superantigens specifically bind to major histocompatibility complex (MHC) II molecules on the surface of antigen presenting cells and the T cell receptor, while cytolysins cause pore formation. For intracellular activity, exotoxins need to be translocated across the eukaryotic membrane. Gram-negative bacteria can directly inject effector proteins in a receptor-independent manner by use of specialized needle apparatus such as bacterial type II, III, or type IV secretion systems. Other methods of translocation include the phagocytic uptake of bacteria followed by toxin secretion, or receptor-mediated endocytosis which allows the targeting of distinct cell types. Receptor-based uptake is initiated by the binding of heteromeric toxin complexes to the cell surface and completed by the translocation of the effector protein(s) across the endosomal membrane. In the cytosol, toxins interact with specific eukaryotic target proteins to cause post-translational modifications that often result in the manipulation of cellular signalling cascades and inflammatory responses. It has become evident that the actions of some bacterial toxins may exceed their originally assumed cytotoxic function. For example, pore-forming toxins do not only cause cytolysis, but may also induce autophagy, pyroptosis, or activation of the MAPK pathways, resulting in adjustment of the host immune response to infection and modification of inflammatory responses both locally and systemically. Other recently elucidated examples of the immunomodulatory function of cell death-inducing exotoxins include TcdB of Clostridium difficile which activates the inflammasome through modification of cellular Rho GTPases, or the Staphyloccocus d-toxin which activates mast cells. The goal of this research topic was to gather current knowledge on the interaction of bacterial exotoxins and effector proteins with the host immune system. The following 16 research and review articles in this special issue describe mechanisms of immune modification and evasion and provide an overview over the complexity of bacterial toxin interaction with different cells of the immune system.