Immunopathological aspects in Human and Bovine Tuberculosis:<br/> - Immunopathological Changes in IRF-8-/- mice during Mycobacterium tuberculosis Infection<br/> - Histopathological and Biomolecular Evaluations in Cattle Tuberculin Skin Test positive slaughtered according to The Regional Eradication Program

Abstract

Among diseases caused by Mycobacteria, tuberculosis remains an unsolved issue in humans and animals, causing economic and public health repercussions. How the host immune system responds at initial stage of infection is the key factor for progression of disease or for the establishment of latent infection. This thesis is focused on two fundamental aspects in the immunopathology of tuberculosis: firstly, in lungs of IRF-8-/- mice histopathologic alterations in both innate and adaptive immune response were observed, after experimental infection of animals with Mycobacterium tuberculosis (Mtb). Secondly, the presence of mycobacteria in carcass of TST positive cattle was investigated during sporadic cases of bTB in Sardinia. To investigate the immune events histochemistry, immunohistochemistry and molecular analysis have been applied. IRF-8 KO mice Mtb-infected showed severe tissue damage in the lungs correlated with an uncontrolled growth of granulomas. In addition, in these animals, an altered inflammatory exudate was observed, constituted by a large number of neutrophils with poor recruitment of lymphocytes, resulting in a higher susceptibility to Mtb infection. In TST cattle, discovering mycobacteria within the carcass using collateral diagnostic methods (histopathology and PCR) have increased the diagnosis of infection of 5% in post-mortem examination. Therefore, for different purposes, investigating the immunopathology in tuberculosis in humans and cattle is even more important in order to perform an earlier diagnosis, aimed to improve better treatment and eradication of disease