Functional transcriptome ofMycobacterium aviumsubsp.paratuberculosisin human macrophage infection and immunological relevance of its specific antigens in type I Diabetes mellitus

Recent studies have identified inMycobacterium aviumsubsp.paratuberculosis(Map) a potential zoonotic agent in the development of some autoimmune diseases in humans. Therefore, it is necessary a thorough understanding ofMap'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 characterizeMap's transcriptome during the infection of human macrophages, the whole gene expression ofMapwas 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 thatMapshifts 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 ofMap(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.