Systemic and pulmonary C1q as biomarker of progressive disease in experimental non-human primate tuberculosis
| Autor: | Nicole V. Borggreven, Karin Dijkman, Simone A. Joosten, Rosalie Lubbers, Tom H. M. Ottenhoff, Leendert A. Trouw, Frank A. W. Verreck |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Tuberculosis lcsh:Medicine Translational immunology chemical and pharmacologic phenomena Disease Article Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Animals lcsh:Science Tuberculosis Pulmonary Multidisciplinary biology business.industry Complement C1q lcsh:R Diagnostic markers medicine.disease biology.organism_classification 3. Good health Complement cascade Experimental models of disease Vaccination Disease Models Animal 030104 developmental biology Immunology Disease Progression Macaca Biomarker (medicine) lcsh:Q Differential diagnosis business Biomarkers Progressive disease 030215 immunology |
| Zdroj: | Scientific Reports Scientific Reports, 10(1). NATURE PUBLISHING GROUP Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-63041-4 |
| Popis: | Tuberculosis (TB) causes 1.6 million deaths annually. Early differential diagnosis of active TB infection is essential in optimizing treatment and reducing TB mortality, but is hampered by a lack of accurate and accessible diagnostics. Previously, we reported on complement component C1q, measured in serum by ELISA, as a candidate biomarker for active tuberculosis. In this work we further examine the dynamics of C1q as a marker of progressive TB disease in non-human primates (NHP). We assessed systemic and pulmonary C1q levels after experimental infection using high or low single dose as well as repeated limiting dose Mycobacterium tuberculosis (Mtb) challenge of macaques. We show that increasing C1q levels, either peripherally or locally, correlate with progressive TB disease, assessed by PET-CT imaging or post-mortem evaluation. Upregulation of C1q did not precede detection of Mtb infection by a conventional interferon-gamma release assay, confirming its association with disease progression. Finally, pulmonary vaccination with Bacillus Calmette Guérin also increased local production of C1q, which might contribute to the generation of pulmonary protective immunity. Our data demonstrate that NHP modelling of TB can be utilized to study the role of C1q as a liquid biomarker in TB protection and disease, complementing findings in TB patients. |
| Databáze: | OpenAIRE |
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