Host-Pathogen Interaction is a privileged area of observation of nature as it is where pathogenic microorganisms and host confront themselves with the common goal of "having success in the world". Microorganisms evolve very rapidly, and very rapidly develop an arsenal of virulence factors that are tailored around key host function. By studying the mechanism of action of microbial virulence factors we can learn about the pathogenesis of the disease caused by the microorganism under study. At the same time we can exploit the "intelligence" of evolution to learn about key physiological functions of the host. Not to say that we can generate novel therapeutics (vaccines, drugs, inhibitors, adjuvants etc.).

This field has increased enormously particularly at the cellular level (1) and, over the years we have learned much about several aspects of cell biology which are specifically modified by virulence factors. Until recently, it appeared that the most sophisticated array of host cell modifications was performed by Yersinia bacteria spp. which inject inside host cells more than a dozen of intracellular toxins. But bacteria never cease to surprise us! Indeed the field of host-pathogen interactions was lighted up by a recent paper reporting major and effective changes of gene expression in Schwann cells (SC) infected by the intracellular pathogen Mycobacterium leprae(Ml) which dedifferentiate them to a mesenchimal stem cell-like status (2). Ml is the agent responsible for the development of leprosy (3), but nowadays few laboratories work with it because of lack of simple animal models and of a fall of the general interest to this disease that can be included among the "neglected ones". But it is not the first time that big news come from forgottent corners (4).

Ml targets rather specifically SC, the glial cells that wrap peripheral nerve with the myelin sheat and cover neuromuscular junctions (5). Ml enter the cell, establish themselves as intracellular pathogens, and then alter the SC inducing their proliferation (the advantage for Ml is evident!) and, at later stages of leprosy, infect skeletal and smooth muscles around the body. How this occurs is not known but this novel study offers a testable model. Masaki et al. used as cellular model SC isolated from adult peripheral nerves and infected them for prolonged period of times in vitro. Using transcriptomics, PCR and immunofluorescence, it was s discovered that the infected SC are extensively reprogrammed by intracellular Ml. Not only SC dedifferentiate by activation of the Erk-signalling pathway, as shown before by the same group, but an entire set of genes are induced. The earliest recorded event is the export of the transcription factor Sox-10 from the nucleus and its degradation. The importance of this event can be understood is one considers that Sox-10 is a major determinant of the SC "personality" including its myelination capacity. SC become proliferative and migratory and redifferentiate into mesodermal cells capable of integrating into muscles, thus explaing the Ml diffusion in these tissues. In addition the infected/reprogrammed cells secretes a cocktail of immune messengers that recruit macrophages that become infected and can further disseminate the bacterium. Masaki et al (2) made an in vitro molecular cell biology study and in vivo extrapolations have to be tested in future studies, but a close inspection of the gene revolution caused by Ml can be very profitable not only for cell biologists, but also for those studing inflammation and regeneration.

1. Cossart P, Boquet P, Normark S, Rappuoli R. Science 271, 315-6 (1996)
2. Masaki T et al Cell 152, 51-67 (2013)
3. Scollard DM et al Clin. Microbiol. Rev. 19, 338-381 (2006)
4. Schiavo G et al Nature 359, 832-5 (1992)
5. Jessen KR & Mirsky R Nat. Rev. Neurosci. 6, 671-682 (2005)