Protein Levels of Pro-inflammatory Cytokines and Chemokines as Biomarkers of Mycobacterium bovis Infection and BCG Vaccination in Cattle

Hamza Khalid, Anouk van Hooij, Tim Connelley, Annemieke Geluk, Jayne Hope

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a globally prevalent infectious disease with significant animal welfare and economic impact. Difficulties in implementing test-and-slaughter measures in low- and middle-income countries (LMICs) and the underperformance of the current diagnostics establish a clear need to develop improved diagnostics. Adaptive immunity biomarkers other than IFNγ could be useful as suggested by various gene expression studies; however, a comprehensive as-sessment at the protein level is lacking. Here, we screened a range of chemokines and cytokines for their potential as biomarkers in samples from M. bovis experimentally challenged or naive animals. Although serum concentrations for most proteins were low, the pro-inflammatory markers, IL-2, CXCL-9, IP-10 and CCL4, in addition to IFNγ, were found to be significantly elevated in bovine tuberculin (PPDb)-stimulated whole blood supernatants. Further assessment of these molecules in BCG-vaccinated with or without subsequent M. bovis challenge or naive animals revealed that PPDb-specific IL-2 and IP-10, in addition to IFNγ, could discriminate naive and BCG-vaccinated from M. bovis challenged animals. Moreover, these proteins, along with CCL4, showed DIVA potential, i.e., enabling differentiation of M. bovis-infected animals from BCG-vaccinated animals. Combined analysis of cytokines and chemokines could also accurately identify M. bovis infection with strong correlations observed between PPDb-specific IFNγ, IL-2 and IP-10 levels. This provides proof of concept for utilizing multiple biomarker signatures for dis-crimination of animals with respect to M. bovis infection or BCG vaccination status.
Original languageEnglish
Article number738
Pages (from-to)1-16
Issue number7
Early online date29 Jun 2022
Publication statusPublished - 29 Jun 2022

Keywords / Materials (for Non-textual outputs)

  • BCG
  • biomarkers
  • bovine tuberculosis
  • cytokines
  • chemokines
  • diagnostics
  • pro-inflammatory


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