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Quantifying Human Monocyte Chemotaxis In Vitro and Murine Lymphocyte Trafficking In Vivo
Published on: October 30, 2017
Differences in monocyte: lymphocyte ratio and Tuberculosis disease progression in genetically distinct populations of
Laura Sibley1, Karen Gooch2, Alice Wareham2
1National Infection Service, Public Health England, Porton Down, Wiltshire, UK. laura.sibley@phe.gov.uk.
Abstract:
Monocyte:lymphocyte ratio (M:L) has been identified as a risk factor in development of TB disease in children and those undergoing treatment for HIV in co-infected individuals. Retrospective analysis was performed using M:L data collected from TB modelling studies performed in Rhesus macaques of Indian genotype (RM), cynomolgus macaque of Chinese genotype (CCM) and cynomolgus macaque of Mauritian genotype (MCM), which found that the more susceptible populations (RM and MCM) had higher M:L ratios than the least susceptible population (CCM). Following Mycobacterium tuberculosis exposure, significant increases in M:L ratio were observed in susceptible RM and MCM within 12 weeks of TB infection, whereas M:L in CCM remained stable, suggesting that changes in M:L ratio may also act as a biomarker of TB disease progression. The frequency of PPD-specific interferon gamma (IFNγ) secreting cells (SFU) were compared, with the more susceptible macaque populations showing an association between M:L and IFNγ SFU frequency. Investigation of the genes associated with monocyte-derived antigen presenting cells revealed differences between RM and CCM, highlighting differences in their monocyte populations, as well as overall M:L ratio. Differences in M:L ratio between macaque populations could be used to explore immunological mechanisms in susceptible populations that would complement human population studies.
Insights
The monocyte:lymphocyte ratio (M:L) may predict tuberculosis (TB) disease progression. Higher M:L ratios were observed in more susceptible macaques following Mycobacterium tuberculosis exposure, suggesting its potential as a biomarker.
Area of Science:
- Immunology
- Infectious Diseases
- Comparative Medicine
Background:
- The monocyte:lymphocyte ratio (M:L) is a known risk factor for tuberculosis (TB) development in children and HIV co-infected individuals.
- Understanding TB pathogenesis and identifying biomarkers for disease progression are critical.
Purpose of the Study:
- To investigate the monocyte:lymphocyte ratio (M:L) as a potential biomarker for TB disease progression in different macaque genotypes.
- To explore differences in M:L ratios and their association with immune responses in TB-susceptible and less susceptible macaque populations.
Main Methods:
- Retrospective analysis of M:L data from TB modeling studies in Rhesus macaques (RM), Chinese cynomolgus macaques (CCM), and Mauritian cynomolgus macaques (MCM).
- Comparison of M:L ratios following Mycobacterium tuberculosis exposure.
- Assessment of PPD-specific interferon gamma (IFNγ) secreting cells (SFU) and gene expression in monocyte-derived antigen presenting cells.
Main Results:
- More susceptible macaque populations (RM and MCM) exhibited higher M:L ratios than the least susceptible population (CCM).
- Significant increases in M:L ratio were observed in susceptible RM and MCM within 12 weeks of TB infection, while CCM remained stable.
- An association was found between M:L ratio and IFNγ SFU frequency in susceptible macaques.
- Genetic differences in monocyte populations were identified between RM and CCM.
Conclusions:
- Changes in M:L ratio may serve as a biomarker for TB disease progression.
- Differences in M:L ratios between macaque populations reflect varying susceptibility to TB.
- These findings in macaques can inform human population studies on TB immunology and pathogenesis.
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