Poster Presentation Lorne Infection and Immunity 2013

HIV infection and age alters monocyte subset proportion and response to LPS. (#101)

Thomas A Angelovich 1 2 , Suzanne M Crowe 1 3 , Peter M Smooker 2 , Anna C Hearps 1 3 , Anthony Jaworowski 1 3
  1. Centre for Biomedical Research, Burnet Institute, Melbourne, VIC, Australia
  2. RMIT University, Melbourne, VIC, Australia
  3. Department of Infectious Disease, Monash University, Melbourne, VIC, Australia

Despite antiretroviral therapy, HIV+ individuals exhibit chronic inflammation and an increased risk of inflammatory age-related diseases such as cardiovascular disease. While the drivers of inflammation remain undefined, both elderly and HIV+ individuals have elevated plasma levels of the potent immune activator lipopolysaccharide (LPS). In response to LPS, monocytes signal via Toll-like receptor-4 to produce proinflammatory cytokines. However, the effect of chronic LPS exposure on monocyte response remains unknown. We hypothesise that prolonged LPS exposure, as observed in ageing and HIV infection, increases monocyte activation and responsiveness which may exacerbate inflammation and the risk of developing inflammatory age-related disease.

Healthy young (<45 years, n=11), elderly (>65, n=8) and young HIV+ (<45, n=17) males were recruited into a cross-sectional study. Activation of Classical (CD14++CD16-), Intermediate (CD14++CD16+) and Non-classical (CD16++CD14+) monocytes was evaluated by measuring basal and LPS-induced (10 ng/mL, 4 h) intracellular IL-6 and TNF production in whole blood by intracellular cytokine staining via flow cytometry.

Both HIV infection and ageing were associated with an expansion of the intermediate (p<0.02) and non-classical monocyte subsets (p<0.05), and a decrease in the proportion of the classical subset. Monocytes from healthy elderly (median 10.84, p=0.002) and young HIV+ (median 13.1, p<0.001) showed increased basal TNF production in comparison to young healthy controls and increased IL-6 and TNF production when stimulated with LPS (p<0.05 for all).

These findings suggest that monocytes from elderly and young HIV+ individuals are chronically activated compared to young, HIV-uninfected controls and shift toward an inflammatory CD16+ phenotype. Identifying the mechanisms driving increased proinflammatory cytokine production from monocytes may provide insight into the causes of chronic inflammation and related inflammatory morbidity in these populations.