HIV infection is associated with altered monocyte subset basal cytokine levels and responsiveness to LPS stimulation. — ASN Events
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HIV infection is associated with altered monocyte subset basal cytokine levels and responsiveness to LPS stimulation. (#215)

Thomas A Angelovich 1 2 , Jingling Zhou 2 , Peter M Smooker 1 , Anna C Hearps 2 3 , Anthony Jaworowski 2 3 4
  1. School of Applied Sciences, RMIT University, Melbourne, Victoria, Australia
  2. Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia
  3. Department of Infectious Disease, Monash University, Melbourne , Victoria, Australia
  4. Department of Immunology, Monash University, Melbourne, Victoria, Australia

Introduction: HIV+ individuals are at increased risk of inflammatory age-related disease despite effective suppression of viremia with combination antiretroviral therapy (cART). Lipopolysaccharide (LPS) is elevated in these individuals and stimulates monocytes via the Toll-like receptor 4 pathway producing IL-6 and TNF. We hypothesise that chronic LPS exposure enhances monocyte response to LPS in HIV+ individuals that exacerbates chronic inflammation and the risk of developing age-related disease.

Methods: The inflammatory state of the three monocyte subsets (classical, intermediate and non-classical) from cART naïve, viremic (n=10) and virologically supressed (VS) HIV+ donors (n=10) was evaluated by measuring basal and LPS-induced (10 ng/mL, 4 h) levels of IL-6 and TNF by whole blood intracellular cytokine staining via flow cytometry and mRNA gene expression and results compared to age-matched HIV- controls (n=10). Soluble signalling components (LPS, LBP), inflammatory markers (CXCL-10) and surface TLR-4 were also measured.

Results: All monocyte subsets from viremic and VS HIV+ individuals showed increased basal levels of intracellular IL-6 and TNF in comparison to HIV- individuals (p<0.001 for all comparisons). Furthermore, these groups showed enhanced IL-6 and TNF production when stimulated with LPS (p<0.05 for all comparisons). While plasma LPS and LBP levels were elevated in HIV+ individuals in comparison to controls (p<0.05 for both), mixing serum from HIV+ individuals with control monocytes did not enhance response to LPS challenge ex vivo suggesting enhanced monocyte response to LPS in HIV+ individuals is governed by mechanisms intrinsic to the monocyte. This is supported by increased surface TLR-4 expression on all monocytes subsets for viremic HIV+ individuals (p<0.05).

Conclusions: Monocytes from HIV+ individuals, regardless of therapy status, show increased basal intracellular IL-6 and TNF levels and a heightened response to LPS which may contribute to chronic inflammation and related inflammatory diseases.