Up-regulation of galectin-3 and its ligands by Trypanosoma cruzi infection with modulation of adhesion and migration of murine dendritic cells.
The impact of a pathogen-induced inflammatory response on dendritic cells (DCs) and on their expression of galectin-3 (Gal-3) was studied on splenic DCs (sDCs) from Trypanosoma cruzi-infected mice. We determined the lectin expression and also presentation of ligands using the labeled galectin as probe. By reverse transcriptase polymerase chain reaction, western blot analysis, quantitative glycocytochemistry, and computer-assisted quantitative microscopy, we demonstrate that, in sDCs from infected mice, expression of Gal-3 and Gal-3-specific ligands were markedly up-regulated and adhesiveness was increased with Gal-3-coated substratum. Gal-3 expression was also enhanced in T. cruzi-infected D2SC-1 cells. To assess influence on migration, we had to work exclusively with D2SC-1 cells because sDCs rapidly lost their capacity to adhere to substratum. Migration of infected- and TCM-treated D2SC-1 cells were reduced when substratum was coated with Gal-3. Expression of Gal-3 by D2SC-1 was reduced when they were incubated with anti-Gal-3 antisense oligonucleotide without effect on cell invasion by the parasite. By using seven neoglycoconjugates, we probed the cellular capacity to specifically bind carbohydrate ligands. Similar to Gal-3, an up-regulation was noted with respect to sites specific for Man and alpha-GalNAc, respectively, revealing that infection-dependent changes are not confined to Gal-3-dependent parameters. Considered together, these data document for the first time that a parasitic infection can modulate both in vivo and in vitro the expression of Gal-3 and of ligands for this lectin in DCs with functional consequences on their capacities of adhesion and migration. These results suggest a new immunomodulatory property of T. cruzi.
Vray
Bernard
B
Laboratoire d'Immunologie Expérimentale, Faculté de Médecine, 808 Route de Lennik, 1070 Brussels, Belgium. bvray@ulb.ac.be
Camby
Isabelle
I
Vercruysse
Vincent
V
Mijatovic
Tatjana
T
Bovin
Nicolai V
NV
Ricciardi-Castagnoli
Paola
P
Kaltner
Herbert
H
Salmon
Isabelle
I
Gabius
Hans-Joachim
HJ
Kiss
Robert
R
D000116:Acetylgalactosamine / Q000378:metabolism; D000818:Animals; D000913:Antibodies, Protozoan / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D037502:Galectin 3 / Q000096:biosynthesis*; D008024:Ligands; D008358:Mannose / Q000378:metabolism; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D011485:Protein Binding; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D000913:Antibodies, Protozoan; D037502:Galectin 3; D008024:Ligands; D020319:Oligodeoxyribonucleotides, Antisense; D000116:Acetylgalactosamine; D008358:Mannose