Present address: Polsinelli Shughart PC, Phoenix, Arizona 85004, USA.
Indoleamine 2,3-dioxygenase (IDO) induced by Leishmania infection of human dendritic cells
Article first published online: 11 SEP 2012
© 2012 Blackwell Publishing Ltd
Volume 34, Issue 10, pages 464–472, October 2012
How to Cite
DONOVAN, M. J., TRIPATHI, V., FAVILA, M. A., GERACI, N. S., LANGE, M. C., BALLHORN, W. and McDOWELL, M. A. (2012), Indoleamine 2,3-dioxygenase (IDO) induced by Leishmania infection of human dendritic cells. Parasite Immunology, 34: 464–472. doi: 10.1111/j.1365-3024.2012.01380.x
- Issue published online: 11 SEP 2012
- Article first published online: 11 SEP 2012
- Accepted manuscript online: 13 JUL 2012 01:45PM EST
- Received: 25 January 2012 Accepted for publication: 3 July 2012
- Indoleamine 2,3-dioxygenase;
- dendritic cell
Dendritic cells (DC) play a pivotal role in regulating immunity, establishing immunologically privileged tissue microenvironments and maintaining homoeostasis. It is becoming increasingly clear that one key mechanism that mediates many DC functions is production of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). For pathogens that cause chronic infection, exploitation of host DCs is a solution to establish and persist within a host. Leishmania parasites cause a range of clinical manifestations, all involving chronic infection, and are proficient at avoiding immune responses. We demonstrate here that infection of human myeloid-derived DC with L. major and L. donovani induces IDO expression using a mechanism that involves autocrine or paracrine stimulation with a DC-secreted factor. Leishmania-induced IDO suppresses allogeneic and tetanus toxoid–specific lymphocyte proliferation, an inhibition that is reversed with the IDO inhibitor, 1-methyl tryptophan (1-MT). Furthermore, IDO expression by human DC does not require live Leishmania infection, as parasite lysates also up-regulate IDO mRNA production. Our data suggest that one mechanism Leishmania parasites utilize to circumvent immune clearance may be to promote the induction of IDO among host DC within the infection microenvironment.