Editorial [Hot Topic: New Strategies and Tools to Identify Drug Targets on Infectious Disorders(Guest Editor: Jose A. Garcia-Sanz)]

In spite the great advances on biomedical sciences, and in particular on the analysis of the immune response regarding cells, mechanisms, signaling pathways and genes involved, together with a plethora of genetically modified animal models, infectious diseases still keep increasing in the world population, both on terms of morbidity and mortality. Naive CD4⁺ T lymphocytes, upon encountering antigen, differentiate towards Th1 or Th2 cells, and the signals leading to the induction of one or the other T cell subset are well known. Similarly, the mechanisms used by CD8⁺cytotoxic T cells to kill their specific targets have been unraveled and conditions leading to the induction of different phenotypes (Tc1, Tc2) established. However, this increased knowledge on immune response mechanisms (both cellular and molecular) has not yet been reflected on the identification of new drug targets to fight infection. The aim of this special issue is to discuss the reasons that might explain, at least in part and form the point of view of the authors, the lack of new drug targets on infectious diseases. The first manuscript by R. Vernal & J.A. Garcia-Sanz discusses two new T lymphocyte subpopulations, namely Th17 cells and regulatory T cells, with a profound impact on the outcome of the T cell responses, analyzing in particular their role in different infections. A manuscript by F. Erard & B. Ryffel follows in which the potential of Toll like receptors as potential drug targets on infectious diseases is discussed. Toll like receptors play a crucial role in the recognition and response to pathogens by the innate immune system. The use of a particular set of TLR could favor a Th1-biased response versus a Th2-biased response, or vice-versa. The following group of manuscripts review several mechanisms that have either been underscored or neglected in the past, all of them with a high impact on T cell activation and acquisition of effector functions. The first is by J. Nakagawa on mRNA stability, where the author describes the relevance of the process, and the current knowledge on the mechanisms involved. The second by O. Villate et al., describes the new increased complexity of the mammalian genomes due to the extensive usage of alternative splicing to generate different isoforms and their role in several diseases. The third one by E. Diaz-Guerra et al., discuss the issue of translational control as a mechanism regulating gene expression and describe evidences not only of the effects of different infections on the translation of the host cell, but also on the own infectious agent. Finally, as a possible application of some of these tools to drug discovery, M. Lopez-Fraga et al., describe the mechanisms of RNA interference and the possible use of siRNA as a new strategy to identify new drug targets.