Flt3 ligand pretreatment promotes protective immunity to Listeria monocytogenes.
Flt3 ligand (Flt3L) plays a critical role in the proliferation, differentiation and survival of haematopoietic progenitor cells. Its potential use in a clinical setting has been suggested. Here, we report that mice administered Flt3L displayed a nine-fold increase in size of their hepatic non-parenchymal cell population and an approximate 365-fold increase in number of mature dendritic cells within their livers. Such mice exhibited an elevated resistance to secondary infections with Listeria monocytogenes, an intracellular bacterial pathogen. More than 2.0 log(10)fewer listeriae were recovered in the livers of Flt3L-treated, than untreated, mice on day 2 following secondary challenge. Importantly, Flt3L-pretreated mice immunized with an avirulent (listeriolysin O-negative) strain of Listeria harbored significantly fewer ( approximately 1.5 log(10)) organisms in their spleens and livers than did control mice immunized with listeriolysin O-negative listeriae and challenged with a lethal dose of bacteria. The latter finding supports a potential role for Flt3L in strategies to develop vaccines to intracellular pathogens.
Gregory
S H
SH
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. sgregory@lifespan.org
Sagnimeni
A J
AJ
Zurowski
N B
NB
Thomson
A W
AW
D000276:Adjuvants, Immunologic; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D022781:Hepatocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007115:Immunization Schedule; D007274:Injections, Intraperitoneal; D008024:Ligands; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000517:prevention & control*; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D001428:Bacterial Vaccines; D008024:Ligands; D008565:Membrane Proteins; D014614:Vaccines, Synthetic; C084881:flt3 ligand protein