Poster Presentation Australasian Society for Immunology Annual Scientific Meeting 2014

Effects of plasma components from Naïve and West Nile virus-infected mice on cellular uptake of immune-modulating microparticles. (#298)

Darren A Cox 1 , Luan Vu 2 , Thomas Ashhurst 2 , Nicholas J.C. King 2
  1. University of Sydney, Camperdown, NSW, Australia
  2. University of Sydney, Camperdown, NSW, Australia

Central nervous system (CNS) infection with neurotropic flavivirus, West Nile (WNV), triggers an immune cascade, culminating in seizures and tissue damage [1, 2]. With only supportive treatment available, the development of immune-modulating therapies is crucial. Immune-modulating microparticles (IMP) sequestrate pathogenic Ly6Chi monocytes in the spleen, away from the foci of infection [3], reducing CNS inflammation and promoting survival, but mechanisms of cell-IMP interaction are undefined. In suspension, 70% of IMP uptake occurs within 5 minutes. We hypothesise interaction is influenced by plasma molecules interacting with various receptors. Uncoated-IMP elicited high uptake by Ly6C+/hi, with 49% more Ly6C+/hi than Ly6C-/lo monocytes from WNV-infected mice taking up uncoated IMP. Furthermore, 87% of monocytes from WNV-infected mice took up >2 IMP, while 69% of naïve cells took up ≤2. Numbers of IMP+ Ly6C+/hi monocytes from naïve- and WNV-infected mice were reduced by 91% and 71%, respectively, if IMP were pre-coated with naïve plasma. In contrast, IMP coated with WNV-infected plasma reduced the numbers of IMP+ Ly6C+/hi monocytes from naïve- and WNV-infected by only 73% and 53%, respectively, while coating IMP with immune plasma inhibited uptake by Ly6C+/hi monocytes from naïve mice by 71%. Similar reductions in IMP uptake were also seen in various cell types, including monocytes, B cells, T cells, eosinophils and neutrophils. Interestingly, in vivo, 40% of IMP+ cells reaching the mesenteric lymph nodes and spleen after i.p administration of IMP were B cells. These findings indicate plasma proteins affect cellular binding to IMP and B cells play an important role in transporting IMP through the lymphatic system to the lymph nodes and spleen. This study provides improved understanding into the mechanisms involved in IMP uptake by cells and will assist in development of therapeutic applications of IMP.

  1. King, N.J., et al., Immunopathology of flavivirus infections. Immunol Cell Biol, 2007. 85(1): p. 33-42.
  2. Lanciotti, R.S., et al., Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science, 1999. 286(5448): p. 2333-7.
  3. Getts, D.R., et al., Therapeutic Inflammatory Monocyte Modulation Using Immune-Modifying Microparticles. Science Translational Medicine, 2014. 6(219): p. 219ra7.