Abstract
BackgroundRecent studies have identified in Mycobacterium avium subsp. paratuberculosis (MAP), already known as a pathogen in ruminants, a potential zoonotic agent of some autoimmune diseases in humans. Therefore, considering the possible risk for public health, 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 and therapeutic tools.ResultsIn order to characterize MAP's transcriptome during macrophage infection, we analyzed for the first time the whole gene expression of a human derived strain of MAP in simulated intraphagosomal conditions and after intracellular infection of the human macrophage cell line THP-1 by using the DNA-microarray technology. Results showed that MAP shifts its transcriptome to an adaptive metabolism for an anoxic environment and nutrient starvation. It up-regulates several response factors to oxidative stress or intracellular conditions and allows, in terms of transcription, a passive surface peptidoglycan spoliation within the macrophage along with an intensification of the anabolic activity for lipidic membrane structures.ConclusionsThese results indicate a possible interactive system between MAP and its host cell based on the internal mimicry unlike other intracellular pathogens, bringing new hypothesis in the virulence and pathogenicity of MAP and its importance in human health.
Highlights
Recent studies have identified in Mycobacterium avium subsp. paratuberculosis (MAP), already known as a pathogen in ruminants, a potential zoonotic agent of some autoimmune diseases in humans
Many studies concerning the transcriptional regulation of macrophages infected by MAP have already been carried out [17,18] by using DNA-microarray technology that has become a useful tool for the study of MAP gene expression under different environmental conditions [19] and during infection of bovine cell lines [20,21]
Differential transcriptome of MAP under acid-nitrosative multi-stress The whole transcriptome of MAP that has been highlighted during the acid-nitrosative stress (Figure 1) was defined by an up-regulation of 510 genes (Additional file 1: Table S1) and a down-regulation of 478 genes (Additional file 1: Table S2) for a total of 988 genes differentially expressed compared to the untreated strain
Summary
Recent studies have identified in Mycobacterium avium subsp. paratuberculosis (MAP), already known as a pathogen in ruminants, a potential zoonotic agent of some autoimmune diseases in humans. Paratuberculosis (MAP), already known as a pathogen in ruminants, a potential zoonotic agent of some autoimmune diseases in humans. Mycobacteria infect mainly macrophage cells [14], for this reason they evolved to develop defense mechanisms to face the hostile environment they encounter within the phagosomal compartment. The molecular mechanism by which the mycobacteria are able to avoid the occurrence of phagolysosome maturation is still unknown For this reason, many studies concerning the transcriptional regulation of macrophages infected by MAP have already been carried out [17,18] by using DNA-microarray technology that has become a useful tool for the study of MAP gene expression under different environmental conditions [19] and during infection of bovine cell lines [20,21]. The characterization of MAP transcriptome during infection of human macrophage cell lines would be of great help in bridging a gap still present in the state of the art for this organism
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