Differences in monocyte: lymphocyte ratio and Tuberculosis disease progression in genetically distinct populations of macaques

Laura Sibley,Stuart Dowall,Anthony Marriott,Philip D Marsh,Mike Dennis,Sally Sharpe,Helen Fletcher,Andrew Chancellor,Andrew D White,Simon Bate,Susan Gray,Alice Wareham,Karen Gooch

doi:10.1038/s41598-019-39819-6

Laura Sibley, Stuart Dowall + Show 11 more

Open Access

https://doi.org/10.1038/s41598-019-39819-6

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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.

Highlights

Laura Sibley1, Karen Gooch1, Alice Wareham1, Susan Gray1, Andrew Chancellor1, Stuart Dowall1, Simon Bate1, Anthony Marriott1, Mike Dennis1, Andrew D
50% of rhesus macaques (RM) were unable to control TB infection, and this was across all doses, outcome was improved with the lowest dose (500–1000 CFU) (Fig. 1b)
M:L ratio was calculated for each of the three macaque populations from individuals enrolled in a variety of studies (Table 1) using data generated using either haematology, or flow cytometry (FC) analysers applied to whole blood (Hemavet and IDEXX haematology analysers and FC), or Peripheral Blood Mononuclear Cells (PBMC) (FC only) (Fig. 2)

Summary

Introduction

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. The ratio of monocytes to lymphocytes defined in peripheral blood has been associated with the outcome of several diseases; including several types of cancer, coronary heart disease, Hepatitis B4, HIV5 and Tuberculosis (TB), among others. M:L has been found to reduce after treatment for HIV, and corresponded with improvement in the patient’s condition5 In humans it appears that the M:L shows promise as an indicator of risk of developing active TB and could facilitate the targeting of preventative treatments/therapy for those who are defined as being at greater risk

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