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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #353919

Research Project: Characterize the Immunopathogenesis and Develop Diagnostic and Mitigation Strategies to Control Tuberculosis in Cattle and Wildlife

Location: Infectious Bacterial Diseases Research

Title: Biomarkers of cell-mediated immunity to bovine tuberculosis

item Thacker, Tyler
item Palmer, Mitchell
item Rabideau, Meaghan
item JONES, GARETH - Animal & Plant Health Agency Apha
item KANIPE, CARLY - US Department Of Agriculture (USDA)
item VORDERMEIER, H - Animal & Plant Health Agency Apha
item Waters, Wade

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/27/2019
Publication Date: N/A
Citation: N/A

Interpretive Summary: Blood is the preferred fluid to diagnose diseases in cattle and humans. This method requires minimal animal handling, usually once, and is minimally invasive. The only blood-based test for tuberculosis in humans and cattle is based on detecting interferon-gamma (IFN-gamma) that is produced in the blood when it is stimulated with proteins from the bacteria, Mycobacterium bovis, that causes tuberculosis. However, interferon-gamma assays do have some disadvantages. The purpose of this report is to determine if other cytokines/chemokines, proteins made by the immune system, could be used in diagnostic tests for tuberculosis. The following cytokines/chemokines were produced in blood from animals that had tuberculosis: IFN-gamma, CXCL9, CXCL10, TNF-alpha, IL-1alpha, IL-1beta, IL-22, IL-21 and IL-13. These were detected by measuring messenger-RNA. IFN-gamma, CXCL9, CXCL10, IL-21 and IL-13 were detected as early as 2 weeks after infection. When detecting proteins, CXCL9 performed in a manner similar to IFN-gamma, making it a potential target for further diagnostic test development. CXCL10 was discovered to be present in the serum from animals before being transported back to the lab for analysis, therefore making it unsuitable for use in a diagnostic test.

Technical Abstract: Whole blood based assays, particularly interferon gamma (IFN-gamma) release assays (IGRAs), are used for the diagnosis of bovine and human tuberculosis (TB). The aim of the current study was to evaluate a panel of cytokines and chemokines for potential use as diagnostic readouts of Mycobacterium bovis (M. bovis) infection in cattle. A gene expression assay was used to determine the kinetics of the response to M. bovis purified protein derivative and a fusion protein consisting of ESAT-6, CFP10, and Rv3615c upon aerosol infection with ~104 cfu of M. bovis. The panel of biomarkers included: IFN-gamma, CXCL9, CXCL10, CCL2, CCL3, TNF-alpha, IL-1alpha, IL-1beta, IL-1Ra, IL-22, IL-21 and IL-13. Protein levels of IFN-gamma, CXCL9, and CXCL10 were determined by ELISA. Findings demonstrate the potential for use of biomarkers beyond IFN-gamma in whole blood assays for the detection of tuberculous cattle.