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Secretome Analysis of Mycobacterial-infected Bovine Macrophages

ABSTRACT: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, a chronic granulomatous disease. Mtb is mostly restricted to humans and seldom causes disease in animals. M. bovis (Mbv) on the other hand causes tuberculosis in cows (bovine tuberculosis) and several wild animals. Each of these pathogens therefore has unique host adaptations and the host- and pathogen-specific factors driving this differential tropism still remain largely unknown. Here we profiled the secretomes of Mtb- and Mbv-infected bovine macrophages to characterise host-specific responses to each pathogen.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Bos Taurus (bovine)

TISSUE(S): Macrophage

DISEASE(S): Tuberculosis

SUBMITTER: Matthias Trost

LAB HEAD: Matthias Trost

PROVIDER: PXD017949 | Pride | 2021-03-11

REPOSITORIES: Pride

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Project description:It is generally accepted that human cancers derive from a mutated single cell. However, the genetic steps characterizing various stages of progression remain unclear. Studying a unique case of metastatic melanoma, we observed that cell lines derived from metachronous metastases arising over a decade retained a central core of genetic stability in spite of divergent phenotypes. In the present study we expanded our previous observations comparing these autologous cell lines of clonal derivation with heterologous ones and correlated array Comparative Genomic Hybridization (aCGH) with gene expression profiling to determine their relative contribution to the dynamics of disease progression. aCGH and gene expression profiling were performed on autologous cell lines and heterologous melanoma cell lines originated from other patients. A striking correlation existed between total extent of genetic imbalances, global transcriptional patterns and cellular phenotypes; they did not follow a strict temporal progression but stemmed independently at various time points from a central core of genetic stability best explained according to the cancer stem cell hypothesis; although their contribution was intertwined, genomic imbalances detectable by aCGH contributed only 25% of the transcriptional traits determining autologous tumors distinctiveness. Our study provides important insights about the dynamics of cancer progression and supports the development of targeted anti-cancer therapies against stable genetic factors determining the individuality of each patientâs disease that are maintained throughout the end stage of disease. Keywords: genetic modification design PBMC from a female donor were Ficoll gradient separated and used throughout the study as reference.. Validation of array CGH accuracy was done by obtaining six additional PBMC from female donors and six PBMC from male donors to confirm stability of gene representation in autosomes and sex-determined imbalances within the X and Y chromosome regions. Five melanoma cell lines were generated from distinct cutaneous melanoma metastases that progressively appeared in patient 888. Other melanoma cell lines were generated from cutaneous melanoma metastases from other patients. The melanoma cell line A375 was purchased from the American Type Culture Collection. For each cell line arrayCGh has been performed.

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Secretome Analysis of Mycobacterial-infected Bovine Macrophages

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