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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #375321
Research Project: Characterize the Immunopathogenesis and Develop Diagnostic and Mitigation Strategies to Control Tuberculosis in Cattle and Wildlife

Location: Infectious Bacterial Diseases Research

Title: Transcriptional profiling of early and late phases of bovine tuberculosis

Author
item ABDELAAL, HAZEM - University Of Wisconsin
item THACKER, TYLER - Animal And Plant Health Inspection Service (APHIS)
item Palmer, Mitchell
item TALAAT, ADEL - University Of Wisconsin

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/29/2021
Publication Date: 12/13/2021
Citation: Abdelaal, H.F., Thacker, T., Palmer, M.V., Talaat, A.M. 2021. Transcriptional profiling of early and late phases of bovine tuberculosis. Infection and Immunity. 90(2). Article e00313-21. https://doi.org/10.1128/iai.00313-21.
DOI: https://doi.org/10.1128/iai.00313-21

Interpretive Summary: Mycobacterium bovis is the cause of tuberculosis in cattle. To better understand the course of disease in cattle we analyzed cells from the blood of cattle infected for 8 weeks (early phase of infection) and 20 weeks (late phase of infection). These cells were tested to determine which genes were increasing in expression compared to genes decreasing in expression. We found the pattern of gene expression in the early phase of infection to be different from that of the late phase. Knowing which genes are expressed during different phases of disease will aid in the development of diagnostic tests to detect bovine tuberculosis at all stages of disease.

Technical Abstract: Bovine tuberculosis caused by Mycobacterium tuberculosis var. bovis (M. bovis) infection, is an important enzootic disease affecting mainly cattle, worldwide. Despite the implementation of national campaigns to eliminate the disease, bovine tuberculosis remains recalcitrant to eradication in several countries. Characterizing the host response to M. bovis infection is crucial for understanding the immunopathogenesis of the disease and for developing better control strategies. To profile the host responses to M. bovis infection, we analyzed the transcriptome of whole blood cells collected from experimentally infected calves with a virulent strain of M. bovis using a Next Generation Sequencing platform (RNAseq). Comparative analysis of animal transcriptomes at early (8 weeks) vs. late (20 weeks) aerosol infection with M. bovis revealed divergent unique profile for each stage of infection. Notably, at the early time point, transcriptional upregulation was observed among several of the top-ranking canonical pathways involved in T-cell chemotaxis. At the late time point, enrichment in the cell mediated cytotoxicity (e.g. Granzyme B) was the predominant host response. These results showed significant change in bovine transcriptional profile and identified arrays of chemokine receptors and monocyte chemoattractant protein (CCL) co-regulated genes that underline the host-mycobacterial interactions during progression of bovine tuberculosis in cattle. Further analysis of the transcriptome profiles identified potential biomarker targets for early and late phases of tuberculosis in cattle. Overall, the identified profiles better characterized identified novel immunomodulatory mechanisms and provided a list of targets for further development onto potential diagnostics for tuberculosis in cattle.