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S72 Immunomodulatory effects of carbon particulates on macrophage handling of streptococcal infections
  1. HL Shaw1,
  2. JC Wallington1,
  3. M Christodoulides1,
  4. DI Phillips2,
  5. TMA Wilkinson1,
  6. KJ Staples1
  1. 1Clinical and Experimental Sciences, University of Southampton, Faculty of Medicine, Southampton, UK
  2. 2MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK

Abstract

Background and objective Airway macrophages are key to a successful immune response to pulmonary infections. Smoke exposure has been previously shown to result in particulate loading of alveolar macrophages and subsequent impaired macrophage responses to infection with Streptococcus pneumoniae.1 Rheumatic heart disease (RHD) is an autoimmune disorder that follows an airway infection with Streptococcus pyogenes in some individuals. Little is understood about the aetiological factors predisposing the development of RHD but smoke exposure from combustion of solid fuels has recently been epidemiologically linked to RHD.

In the context of this epidemiological observation, we hypothesised that smoke exposure would affect macrophage handling of Streptococcus pyogenes in a similar manner to that observed in studies with Streptococcus pneumoniae.

Methods Human positively-isolated CD14+ monocyte-derived macrophages (MDM), an established model for alveolar macrophages, were incubated with an optimised dose of carbon particulates. Phagocytosis of Streptococcus pneumoniae and pyogenes was assessed by bacterial culture of macrophages lysates. Autologous CD3+ T cells were co-cultured with infected MDM for 24 h. Expression of cell surface markers, T cell activation and uptake of FITC beads were assessed by flow cytometry.

Results Phagocytosis of Streptococcus pneumoniae and pyogenes by carbon loaded MDM was impaired compared to non-carbon loaded MDM (18.8% reduction, p = 0.01). Phagocytosis of FITC beads was also shown to be reduced by the carbon loaded MDM (10% reduction, p = 0.03).

Carbon loading decreased MDM surface expression of the phagocytic receptor CD36 (p < 0.01) and decreased the surface expression of antigen presentation molecules HLA-ABC and HLA-DR (p = 0.04 and 0.03 respectively). Addition of S. pyogenes increased expression of HLA-DR only on the cell surface of carbon loaded MDM (p = 0.02). Preliminary results suggest that autologous T cells express IFNγ in response to coculture with infected MDM and that this response is enhanced in carbon loaded MDM.

Conclusion We conclude that carbon exerts immunomodulatory effects on MDM phagocytosis of Streptococcus pyogenes and subsequent antigen presentation. Further investigation of this subject in the context of both chronic lung infection and RHD is therefore warranted.

Reference

  1. Rylance J, et al. Household air pollution causes dose-dependent inflammation and altered phagocytosis in human macrophages. AJRCMB 2015;52(5):584–93.

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