Protein Levels of Pro-Inflammatory Cytokines and Chemokines as Biomarkers of <i>Mycobacterium bovis</i> Infection and BCG Vaccination in Cattle
Bovine tuberculosis (bTB), caused by <i>Mycobacterium bovis</i>, 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 o...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/11/7/738 |
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| author | Hamza Khalid Anouk van Hooij Timothy K. Connelley Annemieke Geluk Jayne C. Hope |
| author_facet | Hamza Khalid Anouk van Hooij Timothy K. Connelley Annemieke Geluk Jayne C. Hope |
| author_sort | Hamza Khalid |
| collection | DOAJ |
| description | Bovine tuberculosis (bTB), caused by <i>Mycobacterium bovis</i>, 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 assessment at the protein level is lacking. Here, we screened a range of chemokines and cytokines for their potential as biomarkers in samples from <i>M. bovis</i> 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 <i>M. bovis</i> challenge or naive animals revealed that PPDb-specific IL-2 and IP-10, in addition to IFNγ, could discriminate naive and BCG-vaccinated from <i>M. bovis</i> challenged animals. Moreover, these proteins, along with CCL4, showed DIVA potential, i.e., enabling differentiation of <i>M. bovis</i>-infected animals from BCG-vaccinated animals. Combined analysis of cytokines and chemokines could also accurately identify <i>M. bovis</i> 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 discrimination of animals with respect to <i>M. bovis</i> infection or BCG vaccination status. |
| first_indexed | 2024-03-09T06:04:26Z |
| format | Article |
| id | doaj.art-801a7b57396647218f11adb2216bcc1a |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-09T06:04:26Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-801a7b57396647218f11adb2216bcc1a2023-12-03T12:05:06ZengMDPI AGPathogens2076-08172022-06-0111773810.3390/pathogens11070738Protein Levels of Pro-Inflammatory Cytokines and Chemokines as Biomarkers of <i>Mycobacterium bovis</i> Infection and BCG Vaccination in CattleHamza Khalid0Anouk van Hooij1Timothy K. Connelley2Annemieke Geluk3Jayne C. Hope4Division of Infection and Immunity, The Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UKDepartment of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDivision of Infection and Immunity, The Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UKDepartment of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDivision of Infection and Immunity, The Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh EH25 9RG, UKBovine tuberculosis (bTB), caused by <i>Mycobacterium bovis</i>, 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 assessment at the protein level is lacking. Here, we screened a range of chemokines and cytokines for their potential as biomarkers in samples from <i>M. bovis</i> 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 <i>M. bovis</i> challenge or naive animals revealed that PPDb-specific IL-2 and IP-10, in addition to IFNγ, could discriminate naive and BCG-vaccinated from <i>M. bovis</i> challenged animals. Moreover, these proteins, along with CCL4, showed DIVA potential, i.e., enabling differentiation of <i>M. bovis</i>-infected animals from BCG-vaccinated animals. Combined analysis of cytokines and chemokines could also accurately identify <i>M. bovis</i> 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 discrimination of animals with respect to <i>M. bovis</i> infection or BCG vaccination status.https://www.mdpi.com/2076-0817/11/7/738BCGbiomarkersbovine tuberculosiscytokineschemokinesdiagnostics |
| spellingShingle | Hamza Khalid Anouk van Hooij Timothy K. Connelley Annemieke Geluk Jayne C. Hope Protein Levels of Pro-Inflammatory Cytokines and Chemokines as Biomarkers of <i>Mycobacterium bovis</i> Infection and BCG Vaccination in Cattle Pathogens BCG biomarkers bovine tuberculosis cytokines chemokines diagnostics |
| title | Protein Levels of Pro-Inflammatory Cytokines and Chemokines as Biomarkers of <i>Mycobacterium bovis</i> Infection and BCG Vaccination in Cattle |
| title_full | Protein Levels of Pro-Inflammatory Cytokines and Chemokines as Biomarkers of <i>Mycobacterium bovis</i> Infection and BCG Vaccination in Cattle |
| title_fullStr | Protein Levels of Pro-Inflammatory Cytokines and Chemokines as Biomarkers of <i>Mycobacterium bovis</i> Infection and BCG Vaccination in Cattle |
| title_full_unstemmed | Protein Levels of Pro-Inflammatory Cytokines and Chemokines as Biomarkers of <i>Mycobacterium bovis</i> Infection and BCG Vaccination in Cattle |
| title_short | Protein Levels of Pro-Inflammatory Cytokines and Chemokines as Biomarkers of <i>Mycobacterium bovis</i> Infection and BCG Vaccination in Cattle |
| title_sort | protein levels of pro inflammatory cytokines and chemokines as biomarkers of i mycobacterium bovis i infection and bcg vaccination in cattle |
| topic | BCG biomarkers bovine tuberculosis cytokines chemokines diagnostics |
| url | https://www.mdpi.com/2076-0817/11/7/738 |
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