Transcriptional response of human dendritic cells to Borrelia garinii--defective CD38 and CCR7 expression detected.
Lyme borreliosis is a disease, which can affect several organs and cause a variety of symptoms. In some patients, the infection may become chronic, even after antibiotic therapy, and cause persisting damage. Dendritic cells (DC) are involved in the initiation of innate and adaptive immune responses. To study interactions between Borrelia garinii (Bg), one of the causative agents of Lyme borreliosis, and human DC, we used a cDNA microarray to compare the Bg-induced DC transcriptional response with the response induced by LPS. The Bg-induced response consisted of a smaller number of genes than the LPS-induced response. The microarray showed that the ectoenzyme CD38, which has an important role in DC chemotaxis and migration to lymph nodes, was strongly up-regulated by LPS but practically not at all by Bg. This finding was confirmed with quantitative RT-PCR and with flow cytometry at the protein level. In addition, RT-PCR showed that CCR7 expression was 11-fold greater in LPS-stimulated than in Bg-stimulated cells. These findings suggest that Bg may affect crucial DC functions by blocking the up-regulation of important molecules in DC migration to lymph nodes, thus affecting further immune responses in Lyme borreliosis infection.
Hartiala
Pauliina
P
Department of Medical Microbiology, University of Turku, Kiinamyllynkatu 13, FI-20520, Turku, Finland. pauliina.hartiala@utu.fi
Hytönen
Jukka
J
Pelkonen
Jenni
J
Kimppa
Katja
K
West
Anne
A
Penttinen
Markus A
MA
Suhonen
Juha
J
Lahesmaa
Riitta
R
Viljanen
Matti K
MK
D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics*; D015748:Borrelia burgdorferi Group / Q000276:immunology* / Q000472:pathogenicity; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000235:genetics*; D014158:Transcription, Genetic / Q000276:immunology*
C515370:CCR7 protein, human; D008070:Lipopolysaccharides; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D051997:ADP-ribosyl Cyclase 1