Transcriptome profile of dendritic cells during malaria: cAMP regulation of IL-6.
Dendritic cells (DCs) have been proposed as mediators of immunity against malaria parasites, as well as a target for inhibition of cellular responses. Here we describe the transcriptomic analysis of spleen DCs in response to Plasmodium infection in a rodent model. We identified a high number of unique transcripts modulated in DCs upon infection. Many cellular functions suffer extensive genomic regulation including the cell cycle, the glycolysis and purine metabolism pathways and also defence responses. Only a small fraction of the regulated genes are coincident with the response induced by other pathogens, suggesting that Plasmodium induces a unique genetic re-programming of DCs. We confirmed regulation of a number of cytokines at the mRNA level including IL-6, IL-10 and IFN-gamma. We further dissected a signalling pathway regulating Plasmodium-induced expression of IL-6 by DCs, which is mediated by release of PGE2, increases in intracellular cAMP and activation of PKA and p38-MAPK.
Carapau
Daniel
D
New York University School of Medicine, Department of Medical Parasitology, 341E. 25th St., New York, NY 10010, USA.
Kruhofer
Mogens
M
Chatalbash
Allison
A
Orengo
Jamie Marie
JM
Mota
Maria Manuel
MM
Rodriguez
Ana
A
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008288:Malaria / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010967:Plasmodium yoelii / Q000472:pathogenicity*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D020543:Proteome; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014158:Transcription, Genetic
D016207:Cytokines; D015850:Interleukin-6; D011506:Proteins; D020543:Proteome; D000242:Cyclic AMP