Effect of Mucosal Cytokine Administration on Selective Expansion of Vaginal Dendritic Cells to Support Nanoparticle Transport

Am J Reprod Immunol. 2015 Oct;74(4):333-44. doi: 10.1111/aji.12409. Epub 2015 Jun 27.

Abstract

Problem: The capacity of antigen-carrying vaccine nanoparticles (NPs) administered vaginally to stimulate local immune responses may be limited by the relatively low numbers of antigen-presenting cells (APCs) in the genital mucosa. Because inflammation is associated with increased susceptibility to sexually transmitted infections, we sought to increase APC numbers without causing inflammation.

Method of study: In this study, we evaluated intravaginal delivery of chemokines, growth factors, or synthetic adjuvants to expand APCs in reproductive tissues.

Results: We found that granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated expansion of CD11b+ dendritic cells (DCs) within 24 hr of intravaginal administration, with no effect on Langerhans cells or macrophages. Expansion of the CD11b+ DC population was not associated with increased inflammatory cytokine production, and these cells retained phagocytic function.

Conclusion: Our data suggest that non-inflammatory expansion of mucosal APCs by intravaginal GM-CSF could be used as an adjuvanting strategy to potentiate the genital immune response to nanoparticulate mucosal vaccines.

Keywords: Cellular expansion; GM-CSF; chemokines; dendritic cells; reproductive mucosa.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intravaginal
  • Animals
  • Biological Transport
  • CD11b Antigen / metabolism
  • Chemokines / pharmacology
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Inflammation / immunology
  • Inflammation / prevention & control
  • Langerhans Cells / cytology
  • Langerhans Cells / immunology*
  • Macrophages / cytology
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mucous Membrane / immunology*
  • Mucous Membrane / metabolism
  • Nanoparticles / metabolism*
  • Vaccines, Synthetic / immunology
  • Vagina / cytology
  • Vagina / immunology*
  • Vagina / metabolism

Substances

  • CD11b Antigen
  • Chemokines
  • ITGAM protein, human
  • Vaccines, Synthetic
  • Granulocyte-Macrophage Colony-Stimulating Factor