Regulation of airway eosinophil and neutrophil infiltration by alpha-galactosylceramide in a mouse model for respiratory syncytial virus (RSV) vaccine-augmented disease.
Respiratory syncytial virus (RSV) is a leading cause of respiratory disease among infants, the elderly and immunocompromised adults. In this study, we assessed the effects of alpha-galactosylceramide, a known immunoregulatory lipid, on liposomal RSV vaccine-induced responses in BALB/c mice subsequently challenged with RSV. Liposomes containing a recombinant fragment of the RSV G protein were prepared with and without alpha-galactosylceramide and used to immunize mice by the intranasal route. The inclusion of alpha-galactosylceramide in the liposomal formulation caused a dramatic reduction in bronchoalveolar lavage neutrophils, but also an increase in eosinophils, following subsequent RSV challenge. The reduction in neutrophils was specific to mice receiving alpha-galactosylceramide-containing liposomes and was not reproduced in mice administered liposomes containing another alpha-galactosyl lipid, alpha-galactosylphosphatidylglyceroylalkylamine. Lung IL-13 mRNA levels were particularly elevated in mice administered alpha-galactosylceramide-containing liposomes followed by RSV challenge. This study demonstrates a striking ability of alpha-galactosylceramide to modulate the cellular airway infiltrate in mice immunized with liposomal RSV vaccine followed by RSV challenge.
Benoit
Anita C
AC
Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada.
Huang
Yan
Y
Maneewatchararangsri
Santi
S
Tapchaisri
Pramuan
P
Anderson
Robert
R
D000818:Animals; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005699:Galactosylceramides / Q000494:pharmacology*; D007377:Interleukin-3 / Q000378:metabolism; D008081:Liposomes; D008168:Lung / Q000473:pathology / Q000821:virology; D008171:Lung Diseases / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology; D011506:Proteins / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000503:physiopathology / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000627:therapeutic use; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000276:immunology*
D005699:Galactosylceramides; D007377:Interleukin-3; D008081:Liposomes; D011506:Proteins; D022261:Respiratory Syncytial Virus Vaccines; C493154:alpha-galactosylceramide