title: Nanoparticles modify dendritic cell homeostasis and induce non-specific effects on immunity to malaria.
abstract: BACKGROUND
  Many current vaccines to a specific pathogen influence responses to other pathogens in a process called heterologous immunity. We propose that their particulate nature contributes to non-specific effects. Herein, we demonstrate polystyrene nanoparticles modulate dendritic cell (DC) homeostasis, thereby promoting a persistent enhanced state of immune readiness to a subsequent infectious challenge.
  
  
  METHODS
  Particles (approximately 40 nm and 500 nm carboxylated polystyrene nanoparticles; PSNPs) alone or conjugated to a model antigen were injected in mice, and DCs in draining lymph nodes (dLNs) and bone-marrow (BM) quantified by flow cytometry. BM cells were tested for capacity to generate DCs upon culture with granulocyte and macrophage colony stimulating factor. Mice were challenged with Plasmodium yoelli. Blood parasitaemias were monitored by GIEMSA. Sera was analyzed for antibodies by ELISA.
  
  
  RESULTS
  Intradermal administration of 40 nm PSNPs induced anti-inflammatory cytokines, chemokines and growth factors, increased numbers and proportions of DCs in the dLN, and increased the capacity of BM to generate DCs. Consistent with these unexpected changes, 40 nm PSNPs pre-injected mice had enhanced ability to generate immunity to a subsequent malarial infection.
  
  
  CONCLUSIONS
  Intradermal administration of 40 nm PSNPs modifies DC homeostasis, which may at least in part explain the observed beneficial heterologous effects of current particulate vaccines. Further nanotechnological developments may exploit such strategies to promote beneficial non-specific effects.
authors.affiliation: Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, 89 Commercial Road, Melbourne, Victoria 3004, Australia Magdalena.Plebanski@monash.edu Sue.Xiang@monash.edu.
authors.forename: Sue D
authors.initials: SD
authors.lastname: Xiang
authors.affiliation: Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, 89 Commercial Road, Melbourne, Victoria 3004, Australia.
authors.forename: Ying Y
authors.initials: YY
authors.lastname: Kong
authors.affiliation: Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, 89 Commercial Road, Melbourne, Victoria 3004, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hanley
authors.affiliation: Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, 89 Commercial Road, Melbourne, Victoria 3004, Australia.
authors.forename: Martina
authors.initials: M
authors.lastname: Fuchsberger
authors.affiliation: Burnet Institute, 85 Commercial Road, Melbourne, Victoria 3004, Australia.
authors.forename: Blessing
authors.initials: B
authors.lastname: Crimeen-Irwin
authors.affiliation: Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, 89 Commercial Road, Melbourne, Victoria 3004, Australia Magdalena.Plebanski@monash.edu Sue.Xiang@monash.edu.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D006706:Homeostasis; D018796:Immunoconjugates / Q000494:pharmacology; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D014614:Vaccines, Synthetic / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D018796:Immunoconjugates; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic
keywords: Bone marrow; Dendritic cells; Malaria; Nanoparticle; Non-specific; Vaccine