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Published online before print April 19, 2006

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1205742

Received for publication December 19, 2005.
Revised February 16, 2006.
Accepted for publication February 27, 2006.

Article

Differential responsiveness to IFN- and IFN- of human mature DC through modulation of IFNAR expression

Martina Severa ^*, Maria Elena Remoli ^*, Elena Giacomini ^*, Josiane Ragimbeau , Roberto Lande ^*, Gilles Uzé , Sandra Pellegrini , and Eliana M. Coccia ^*@

*Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; CNRS UMR 5124, Montpellier, France; and Unit of Cytokine Signaling, CNRS URA 1961, Institut Pasteur, Paris, France

^@ To whom correspondence should be addressed. E-mail: coccia{at}iss.it.

	Abstract

In human monocyte-derived dendritic cells (DC), infection with Mycobacterium tuberculosis and viruses or stimulation with Toll-like receptor-3 and -4 agonists causes the release of type I interferon (IFN). Here, we describe that the IFN- released upon stimulation with lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly I:C) is responsible for a rapid and sustained signal transducer and activator of transcription-1 and -2 activation and expression of IFN-stimulated genes, such as the transcription factor IFN regulatory factor-7 and the chemokine CXC chemokine ligand 10. The autocrine production of IFN- from LPS and poly I:C-matured DC (mDC) induced a marked decline in the level of the two IFN receptor (IFNAR) subunits. It is interesting that we found that upon clearing of the released cytokines, LPS-stimulated DC reacquired full responsiveness to IFN- but only partial responsiveness to IFN-, and their maturation process was unaffected. Monitoring of surface and total levels of the receptor subunits showed that maximal expression of IFNAR2 resumed within 24 h of clearing, and IFNAR1 expression remained low. Thus, mDC can modulate their sensitivity to two IFN subtypes through a differential regulation of the IFNAR subunits.

Key Words: type I IFN • cytokine receptor • TLR • LPS

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