Poster Presentation Lorne Infection and Immunity 2014

Marked changes in toll-like receptor expression & function in a cohort of patients with active tuberculosis in Melbourne, Australia (#128)

Sabine De Silva 1 2 , Grant Jenkin 2 , Kumar Visvanathan 1 2 3
  1. Centre for Inflammatory Diseases, Department of Medicine, Monash University, Melbourne, Victoria, Australia
  2. Department of Infectious Diseases, Monash Health, Melbourne, VIC, Australia
  3. Immunology Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia
The human host’s innate immune responses involved in tuberculosis (TB) are central to the recognition and control of the infection (1). Toll-like receptors (TLRs) are an important part of this process, although their role, especially in humans is not yet fully defined (2-3). We aim to characterise TLR expression and function in patients with TB and examine the effect of anti-tuberculous therapy. Patients with active TB had blood samples taken during antimicrobial therapy (baseline, 1 month, 2 months and end-of-treatment). Active TB was defined by positive culture, PCR or if presumed clinically. TLR expression (TLR2,4 and 7/8) on peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry. Cytokine levels (TNFα, IL-6) using ELISA were measured following stimulation of PBMCs with TLR-ligands to determine function. Preliminary data of the first 14 patients with active TB is presented here. TLR expression: There was a significant decrease in TLR4 expression (p value=0.0391) and a trend to decreased TLR2 expression (p=0.0547) on CD14+ monocytes after treatment. TLR7 expression increased in these cells when comparing early and end-of treatment (p=0.0391). Interestingly, there was a trend to an increase in TLR7 expression when comparing early and end-of treatment samples in NKT cells (CD3+, CD56+) and CD56dim NK cells (p=0.0547-0.0742 respectively). Stimulated Cytokine measurements: TNFα levels increased significantly between baseline, early and end-of treatment following stimulation with TLR9 ligand CpG (p=0.021 – p=0.0498), and without stimulation (p=0.0156 - p=0.0313). IL-6 levels were also significantly increased between baseline and end-of treatment (p=0.0039) following stimulation with TLR9 ligand. Conclusions: The differences in TLR expression and cytokine levels in this pilot study highlight the potential of utilising these to form a better understanding of longitudinal changes following anti-microbial therapy in active TB. Our findings suggest that measurement of innate immune responses may provide a means of measuring treatment responses.
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  2. (2) Hiroyuki S. et al, (2011). Clinical and developmental immunology 2011(Article ID 347594).
  3. (3) Druszczynska M et al (2011). Tuberculosis:Immunology, Cell Biology and Novel Vaccination Strategies. Vancouver, Canada.