Effects of alveolar macrophage depletion on liposomal vaccine protection against respiratory syncytial virus (RSV)

Clin Exp Immunol. 2006 Jul;145(1):147-54. doi: 10.1111/j.1365-2249.2006.03114.x.

Abstract

Little is known about the identities and roles of antigen-presenting cells upon exposure to antigens of respiratory syncytial virus (RSV). Here, we focused on elucidating the importance of alveolar macrophages in conferring protective immunity in mice administered a liposome-encapsulated recombinant fragment of the RSV G protein. Mice were depleted of alveolar macrophages by intranasal inoculation of liposome-encapsulated dichloromethylenediphosphonic acid (DMDP). Mice depleted of alveolar macrophages prior to immunization developed reduced levels of serum RSV-neutralizing antibody and showed dramatically impaired protection against RSV challenge. The severity of interstitial inflammation was also markedly reduced in macrophage-depleted mice. In conclusion, this study demonstrates a pivotal role for alveolar macrophages during exposure to liposome-encapsulated RSV antigen in initiating both protective and histopathological responses against RSV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Clodronic Acid / pharmacology
  • Dendritic Cells / immunology
  • Liposomes
  • Lung / pathology
  • Lung / virology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / pathology
  • Macrophages, Alveolar / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Neutrophils / immunology
  • Recombinant Fusion Proteins / administration & dosage
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / pathology
  • Respiratory Syncytial Virus Vaccines / administration & dosage*
  • Respiratory Syncytial Viruses*
  • Thioredoxins / genetics
  • Vaccination

Substances

  • Liposomes
  • Recombinant Fusion Proteins
  • Respiratory Syncytial Virus Vaccines
  • Clodronic Acid
  • Thioredoxins