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This research would not have been possible without the support of many people and institutions. I would like to express my deepest gratitude to my adviser, professor Jose Manuel Vassallo M., for his guidance, useful comments, and remarks. He has encouraged me in the development of this thesis and helped making some sense of the results after lengthy meetings in his office. Also, I would like to thank many people here in Spain, to the chair in Transport Economics (UPM-INECO), to the group of colleagues in the Transportation Research Center ─TRANSyT, to the director, and to the administrative staff who have been instrumental in the successful completion of this research.Also, I would like to show my greatest appreciation to my professor, boss and friend Santiago Henao Perez head of the Center for Roads and Transport Studies in the Colombian School of Engineering Julio Garavito (Bogota -Colombia) for his motivation, tremendous support, experience and help over the last fifteen years. Without his encouragement and guidance, I would not have followed his steps to study outside of Colombia. Furthermore, I thank to the Colombian School of Engineering Julio Garavito, to the rector, to my colleagues, and to the different board levels. I would like to thank also to the many students that I have met in my classes since 2000 because they have constantly motivated and aimed at advancing in the transportation field. Additionally, I would like to thank to the consultant's colleagues that I have met in different projects in Colombia and outside where I have applied most of my academic experience, but where I have also approximate the real life to the academic context. Finally, I thank to COLFUTURO for their support on the way. I am most especially grateful to my loved ones (Juan Sebastián, and Mónica), who have supported me throughout this period by giving extraordinary courage. I will be grateful forever for their accompaniment over these years in Spain. Also, I am indebted to the rest of my family and my cousins for their constant support and help.

Interleukin (IL)-17D is a cytokine in the IL-17 family that is conserved in vertebrates and invertebrates. In contrast to IL-17A, which is expressed in T cells, IL-17D is expressed broadly in non-immune cells. IL-17D can promote immune responses to cancer and viruses in part by inducing chemokines that recruit natural killer cells and neutrophils. Although bacterial infection can induce IL-17D in other species, the role of mammalian IL-17D in anti-bacterial immunity has not been determined. In order to ascertain whether IL-17D has a role in mediating immunity against bacterial infections, we studied intraperitoneal infection by Group A Streptococcus (GAS) S. pyogenes in wild-type (WT) and IL-17D-deficient mice. We found that there was more weight loss and decreased survival in mice deficient in IL-17D compared to WT animals after GAS infection. In addition, IL-17D deficient animals had increased bacterial burden in the kidney and peritoneal cavity after GAS infection compared to WT animals. In WT animals, IL-17D transcript could be induced by GAS infection, correlating with increased levels of the chemokine CCL2 and neutrophil recruitment. Notably, GAS-mediated induction of IL-17D seemed to require live bacteria, indicating that pattern recognition did not mediate induction of IL-17D. Altogether, our results demonstrate a role for IL-17D in sensing replicating bacteria and inducing immune responses important in clearing bacteria in distant organs.

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