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Recognition of host-protective immune activation by Mycobacterium tuberculosis

ABSTRACT: The cytokine interferon-γ is a principal effector of macrophage activation and immune resistance to mycobacterial infection; however, pathogenic mycobacteria are capable of surviving in interferon-γ-activated macrophages by largely unknown mechanisms. We found that interferon-γ specifically bound to pathogenic mycobacteria and enhanced their growth in culture. Proteomic and electron microscopy analyses revealed that interferon-γ directly triggers proliferative activity and virulence phenotype in pathogenic mycobacteria that allow them to survive and grow inside macrophages. These findings suggest that pathogenic mycobacteria may have evolved eukaryotic-like signal transduction mechanisms to recognize host-protective immune activation.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mycobacterium Bovis Bcg Str. Pasteur 1173p2 Bacteria

DISEASE(S): Pulmonary Tuberculosis

SUBMITTER: Hsin-Yi Wu

LAB HEAD: Huynh Tan Hop

PROVIDER: PXD038542 | Pride | 2024-09-05

REPOSITORIES: Pride

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			Action	DRS
	20220416_1078_NCKUPCLiao_Hop-1.msf	Msf
	20220416_1078_NCKUPCLiao_Hop-1.raw	Raw
	20220416_1080_NCKUPCLiao_Hop-2.msf	Msf
	20220416_1080_NCKUPCLiao_Hop-2.raw	Raw
	20220416_1082_NCKUPCLiao_Hop-3.msf	Msf

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Project description:Background: Mycobacterium avium subspecies paratuberculosis (MPTb) is the causative agent of Johne’s disease, an intestinal disease of ruminants with major economic consequences. MPTb bacilli are phagocytosed by host macrophages upon exposure where they persist, resulting in lengthy subclinical phases of infection that can lead to immunopathology and disease dissemination. Consequently, analysis of the macrophage transcriptome in response to MPTb infection can provide valuable insights into the molecular mechanisms that underlie Johne’s disease. Here, we investigate pan-genomic gene expression in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro infection with MPTb (multiplicity of infection 2:1) at intervals of 2 hours, 6 hours and 24 hours post-infection. Results: Differentially expressed genes were identified by comparing the transcriptomes of the infected MDM to the control MDM at each time point (adjusted P-value threshold ≤ 0.10). 1,050 differentially expressed unique genes were identified 2 hours post-infection, with 974 and 84 differentially expressed unique genes detected 6 hours and 24 hours post-infection, respectively. Furthermore, in the infected MDM the number of upregulated genes exceeded the number of downregulated genes at each time point, with the fold-change in expression for the upregulated genes markedly higher than that for the downregulated genes. Conclusions: Inspection and systems analysis of the differentially expressed genes revealed changes in the expression profiles of genes involved in the inflammatory response, cell signalling pathways and apoptosis. The transcriptional changes associated with cellular signalling and the inflammatory response may reflect different immuno-modulatory mechanisms that underlie host-pathogen interactions during infection. Affymetrix GeneChip® Bovine Genome Arrays were used to examine gene expression of bovine monocyte-derived macrophages (MDM) after in vitro challenge with Mycobacterium avium subspecies paratuberculosis across a time series of 2 hr, 6 hr and 24 hr post-challenge. A 0 hr control treatment was also generated and seven different age-matched female Holstein-Friesian cattle were used for each time-point/treatment combination for a total of 49 microarrays, one of which was excluded from analysis since it did not pass quality control.

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Recognition of host-protective immune activation by Mycobacterium tuberculosis

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