Project description:The upsurge of multidrug-resistant infections has rendered tuberculosis the principal cause of death among infectious diseases. A clonal outbreak multidrug-resistant triggering strain of Mycobacterium tuberculosis was identified in Kanchanaburi Province, designated “MKR superspreader”, which was found to subsequently spread to other regions, as revealed by prior epidemiological reports in Thailand. Herein, we showed that the MKR displayed a higher growth rate upon infection into host macrophages in comparison with the H37Rv reference strain. To further elucidate the MKR’s biology, we utilised RNA-Seq and differential gene expression analyses to identify host factors involved in the intracellular viability of the MKR. A set of host genes function in the cellular response to lipid pathway was found to be uniquely up-regulated in host macrophages infected with the MKR, but not those infected with H37Rv. Within this set of genes, the IL-36 cytokines which regulate host cell cholesterol metabolism and resistance against mycobacteria attracted our interest, as our previous study revealed that the MKR elevated genes associated with cholesterol breakdown during its growth inside host macrophages. Indeed, when comparing macrophages infected with the MKR to H37Rv-infected cells, our RNA-Seq data showed that the expression ratio of IL-36RN, the negative regulator of the IL-36 pathway, to that of IL-36G was greater in macrophages infected with the MKR. Furthermore, the intracellular survival of MKR was diminished with decreased IL-36RN expression. Overall, our results indicate that IL-36RN is critical for MKR intracellular survival and could serve as a new target against this emerging multidrug-resistant M. tuberculosis strain.
Project description:Tuberculosis continues as an important public health problem. Particularly considering Beijing-family strains of Mycobacterium tuberculosis, which have been associated with drug-resistance and hypervirulence. The Beijing-like SIT190 (BL) is the most prevalent Beijing strain in Colombia. The pathogenic mechanism and immune response against this pathogen is unknown. Thus, we compared the course of pulmonary TB in BALB/c mice infected with Classical-Beijing strain 391 and BL strain 323. The disease course was different among infected animals with Classical-Beijing and BL strain. Mice infected with BL had a 100% mortality at 45 days post-infection (dpi), with high bacillary loads and massive pneumonia, whereas infected animals with Classical-Beijing survived until 60 dpi and showed extensive pneumonia and necrosis. Lung RNA extraction was carried out at early (day 3 dpi), intermediate (day14 dpi), and late (days 28 and 60 dpi) time points of infection. Transcriptional analysis of infected mice with Classical-Beijing showed several over-expressed genes, associated with a pro-inflammatory profile, including those for coding for CCL3 and CCL4 chemokines, both biomarkers of disease severity. Contrary, mice infected with BL displayed a profile which included the over-expression of several genes associated with immune- suppression, including Nkiras, Dleu2 and Sphk2, highlighting an anti-inflammatory milieu which would allow high bacterial replication followed by an intense inflammatory response. In summary, both Beijing strains induced a non-protective immune response which induced extensive tissue damage, BL strain induced rapidly extensive pneumonia and death, whereas Classical-Beijing strain produced slower extensive pneumonia later associated with extensive necrosis.
Project description:This SuperSeries is composed of the following subset Series: GSE6209: The global transcriptional profile of Mycobacterium tuberculosis during human macrophages infection GSE7962: Sigma factor E of Mycobacterium tuberculosis controls the expression of bacterial components that modulate macrophages Keywords: SuperSeries Refer to individual Series
Project description:Characterisation of blood and lung global transcriptional responses to Mycobacterium tuberculosis infection in distinct mouse models of Tuberculosis
Project description:Characterisation of blood and lung global transcriptional responses to Mycobacterium tuberculosis infection in distinct mouse models of Tuberculosis
Project description:Analysis of Metfromin induced changes in the lung cells of Mycobacterium tuberculosis infected mouse at gene expression level. The hypothesis tested in the present study was whether metformin has any effect on the host immune response in Mycobacterium tuberculosis infected mice? Results provide important information on the effect of metformin on the inflammatory response and immune activation associated with mycobacterial infection. In conclusion, Metfromin normalizes the chronic inflammation associated with Mycobacterium tuberculosis infection.
Project description:Analysis of mesenchymal stell cell gene expression level upon Mycobacterium tuberculosis infection. Transcriptome landscape provide important information of the response of stem cell infetion with Mycobacterium tuberculosis such as antibacterial pathways and specific anabolic/catabolic cellular functions.
Project description:Characterisation of blood and lung global transcriptional responses to Mycobacterium tuberculosis infection in distinct mouse models of Tuberculosis
Project description:Characterisation of blood and lung global transcriptional responses to Mycobacterium tuberculosis infection in distinct mouse models of Tuberculosis
Project description:Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic in the context of house hold contacts.
