Research Article Modulation of Stat-1 in Human Macrophages Infected with Different Species of Intracellular Pathogenic Bacteria Giuditta Fiorella Schiavano, 1 Sabrina Dominici, 2 Laura Rinaldi, 1 Alfonsina Mariarosaria Cangiano, 2 Giorgio Brandi, 1 and Mauro Magnani 2 1 Department of Biomolecular Sciences, Section of Toxicological, Hygienic and Environmental Sciences, University of Urbino Carlo Bo, Via S. Chiara 27, 61029 Urbino, Italy 2 Department of Biomolecular Sciences, Section of Biochemistry and Molecular Biology, University of Urbino Carlo Bo, Via Saf 2, 61029 Urbino, Italy Correspondence should be addressed to Giuditta Fiorella Schiavano; giuditta.schiavano@uniurb.it Received 19 April 2016; Accepted 8 June 2016 Academic Editor: Manoj K. Mishra Copyright © 2016 Giuditta Fiorella Schiavano et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Te infection of human macrophages by pathogenic bacteria induces diferent signaling pathways depending on the type of cellular receptors involved in the microorganism entry and on their mechanism(s) of survival and replication in the host cell. It was reported that Stat proteins play an important role in this process. In the present study, we investigate the changes in Stat-1 activation (phosphorylation in p-tyr 701 ) afer uptake of two Gram-positive (Listeria monocytogenes and Staphylococcus aureus) and two Gram-negative bacteria (Salmonella typhimurium and Legionella pneumophila) characterized by their varying abilities to enter, survive, and replicate in human macrophages. Comparing the results obtained with Gram-negative and Gram-positive bacteria, Stat-1 activation in macrophages does not seem to be related to LPS content. Te p-tyr 701 Stat-1 expression levels were found to be independent of the internalized bacterial number and IFN- release. On the contrary, Jak/Stat-1 pathway activation only occurs when an active infection has been established in the host macrophage, and it is plausible that the diferences in the expression levels of p-tyr 701 Stat-1 could be due to diferent survival mechanisms or to diferences in bacteria life cycles within macrophages. 1. Introduction Intracellular bacterial pathogens are a group of microor- ganisms that have developed many abilities to survive and replicate in mammalian cells [1]; thus, they are protected from the defense mechanisms of the host, such as specifc antibodies and complement, making their exposition to antimicrobial agents more difcult. As a consequence, they are one of the major causes of global morbidity and mortality. Although any type of tissue cells potentially serves as a habitat, for most intracellular bacteria, the macrophage rep- resents the typical host cell. Indeed, although macrophages contribute to the frst line of defense against infection through phagocytosis, paradoxically, in host-pathogen interactions, they can also become a reservoir for several pathogenic bacteria. Tis occurs because these pathogens have evolved to reside within the hostile environment of macrophages and are able to avoid host cell death. When macrophages make contact with bacteria, several signal-transduction pathways are activated [2] stimulating phagocytosis. Tis cellular function is extremely complex, and no single model can fully account for the diverse kind of microorganisms that enter macrophages. In fact, difer- ent bacteria-recognition receptors induce diferent signaling pathways according to the type of cellular receptors called into play by microorganism entry. Te signal transducer and activator of transcription 1 (Stat-1) is an indispensable component of the cellular response to interferons (IFNs) during the immune reaction to pathogens. In fact, interferons employ receptor-associated Janus kinases (Jaks) to activate Stats by tyrosine phosphory- lation [3]. Hindawi Publishing Corporation Journal of Immunology Research Volume 2016, Article ID 5086928, 8 pages http://dx.doi.org/10.1155/2016/5086928