Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana
Monocyte transcriptome signatures of inflammation and enhance neutrophil recruitment characterize immunopathology in the blood of tuberculosis patients
Poster Abstract
Tuberculosis (TB) is characterized by immunopathology in the blood and monocytes have been shown to be highly sensitive to plasma environment changes in TB patients. Here, we investigated TB plasma effects on ‘reference monocytes’ using RNA sequencing to characterize a potential immunomodulatory role of monocytes in TB. Candidate pathways induced by plasma samples from TB patients (n=99) compared to healthy controls (n=62) were analyzed for changes in signal transduction, phenotype and secreted cytokines by flow cytometry. Finally, potential implications were characterized in blood samples from corresponding patients and controls.
Reference monocytes treated with TB plasma showed an enrichment of pathways involved in inflammation and chemotaxis. Inflammatory cytokines were accompanied by enhanced phosphorylation of STAT molecules (i.e., STAT1/3/5), and strong positive correlations were detected for Interleukin (IL)-6 only in TB plasma-treated monocytes. Moreover, monocyte chemokine receptors (i.e., CCR-1, CCR-5) and pro-inflammatory chemokines (i.e., CXCL-1, CXCL-2, CXCL-8, G-CSF, CCL-2) that attract granulocytes and monocytes were significantly higher in TB plasma-treated monocytes. Notably, corresponding clinical samples also showed higher plasma levels for a subset of inflammatory cytokines/chemokines and, in particular, high IL-6 levels correlated positively with accumulation of neutrophil granulocytes in the blood of TB patients. Finally, monocytes from TB patients were characterized by increased chemokine receptor expression, higher proportions of a CCR-2+ subpopulation and aberrant high SOCS3 expression.
These results suggest that monocytes may play a significant role in amplifying plasma immunopathology, leading to sustained mobilization and accumulation of neutrophil granulocytes and chronic inflammation in the blood of TB patients.
Biography
Millicent is a research assistant at the Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), working with Professor Richard O. Phillips. She holds a BSc in Biological Sciences and an MPhil in Clinical Microbiology from Kwame Nkrumah University of Science and Technology. Her research focuses on infection immunology, with a current emphasis on understanding the immunological mechanisms of mycobacterial infections, particularly identifying immunopathognomonic markers for acute tuberculosis. Millicent has experience in study planning and implementation, especially in resource-limited settings. Her expertise includes flow cytometry, PCR, and ELISA. She also has intermediate skills in bioinformatics and R.