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Infection and Immunity, January 2004, p. 89-93, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.89-93.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Selective Induction of Tumor Necrosis Receptor Factor 6/Decoy Receptor 3 Release by Bacterial Antigens in Human Monocytes and Myeloid Dendritic Cells

Sunghee Kim,1,{dagger} William J. McAuliffe,1 Liubov S. Zaritskaya,1 Paul A. Moore,1 Lurong Zhang,2 and Bernardetta Nardelli1*

Human Genome Sciences Inc., Rockville, Maryland 20850,1 Lombardi Cancer Center, Washington, D.C. 200642

Received 30 June 2003/ Returned for modification 4 August 2003/ Accepted 30 September 2003

Tumor necrosis factor (TNF) receptor 6/decoy receptor 3 (TR6/DcR3) is an antiapoptosis soluble receptor of the TNF family produced by tumor cells. In this study, TR6 expression in human immune cells was investigated. TR6 mRNA and protein were detectable in selected antigen-presenting cells. Monocytes and myeloid-derived dendritic cells (MDC) released the protein exclusively following stimulation of Toll-like receptor 2 (TLR2) and TLR4 by gram-positive and gram-negative bacterial antigens. Plasmacytoid dendritic cells, activated by bacterial antigens via TLR9 or by viral infection, did not produce the protein. Similarly, activated T cells did not release TR6. The release of TR6 by MDC was dependent on the activation of p42/p44 mitogen-activated protein kinases, Src-like protein tyrosine kinases, and phosphatidylinositol 3-kinase, signaling pathways important for MDC maturation and survival. In agreement with the in vitro data, TR6 levels in serum were significantly elevated in patients with bacterial infections. Overall, these data suggest a novel role for TR6 in immune responses to bacteria.

* Corresponding author. Mailing address: Human Genome Sciences Inc., 9800 Medical Center Dr., Rockville, MD 20850. Phone: (240) 314-4400. Fax: (301) 340-7159. E-mail: bernardetta_nardelli{at}hgsi.com.

Editor: F. C. Fang

{dagger} Present address: Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487.

Infection and Immunity, January 2004, p. 89-93, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.89-93.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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