Host Detection of Pathogen-Induced Translational Inhibition: A New Pathogen-Specific Branch of the Innate Immune System?

Abstract

Both intracellular and extracellular pathogens ultimately disrupt processes inside the host cell to cause disease. While extracellular pathogens remain outside of the cell, they use a myriad of methods to deliver toxins into host cells, either directly with their own secretion systems or indirectly by exploiting host endocytosis. The AB toxins are a class of secreted bacterial proteins that have been studied extensively for the mechanisms by which they disrupt host processes, as well as their route of entry into host cells [1]. For example, exotoxin A (ToxA), an AB toxin produced by the bacterial pathogen Pseudomonas aeruginosa, was shown to enter host cells by receptor-mediated endocytosis in 1980 [2]. Once inside of cells, ToxA inactivates the host elongation factor EF2 to block host mRNA translation. ToxA is one of several bacterial toxins, including Diphtheria toxin and Shiga toxin, which act to block translational elongation. The host response to these toxins has been poorly explored until recently, when it was shown that the translation-blocking effects of these toxins can switch on a form of host defense termed ‘surveillance immunity’ [3–5] that is part of a framework for host responses called ‘patterns of pathogenesis’ [6,7]. This pathogen-specific immunity is part of an emerging branch of the host defense that is critical for survival of nonprofessional immune cells, and may be important for professional immune cells as well.