Cossu, Andrea (2012) Functional transcriptome of Mycobacterium avium subsp. paratuberculosis in human macrophage infection and immunological relevance of its specific antigens in type I Diabetes mellitus. Doctoral Thesis.
Recent studies have identified in Mycobacterium avium subsp. paratuberculosis (Map) a potential zoonotic agent in the development of some autoimmune diseases in humans. Therefore, it is necessary a thorough understanding of Map's gene expression during infection of human host as well as the identification of its immunogenic and/or virulence factors for the development of appropriate diagnostic or therapeutic tools. In order to characterize Map's transcriptome during the infection of human macrophages, the whole gene expression of Map was analyzed with DNA-microarray technology in simulated intraphagosomal conditions created with an acid-nitrosative culture preparation and after intracellular infection of the human macrophage cell line THP-1. Results showed that Map shifts its transcriptome to an adaptive metabolism for an anoxic environment and nutrient starvation, up-regulating several response factors to oxidative stress or intracellular conditions and allowing a passive surface peptidoglycan spoliation within the macrophage. Additionally, the presence of antibodies against two specific proteins of Map (MptD and MAP3738c) was investigated in sera of patients affected by type 1 Diabetes mellitus (T1DM) and type 2 Diabetes mellitus (T2DM). Results showed a positive response to both proteins in T1DM patients whereas no difference with controls was found for T2DM patients suggesting a potential association between T1DM and the bacterial infection.
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