HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Athié-Morales, V. Articles by Gardiner, C. M. PubMed PubMed Citation Articles by Athié-Morales, V. Articles by Gardiner, C. M.

Activation of Human NK Cells by the Bacterial Pathogen-Associated Molecular Pattern Muramyl Dipeptide

Verónica Athié-Morales^*, Geraldine M. O’Connor and Clair M. Gardiner^1,

^* Xoma Ireland Limited and School of Biochemistry and Immunology, Trinity College, Dublin, Ireland

Muramyl dipeptide (MDP) is a bacterial pathogen associated molecular pattern derived from both Gram-positive and -negative bacteria. It is a specific ligand for nuclear oligomerization domain 2, a pattern recognition receptor best characterized for its role in immunosurveillance in the gut. In this study, we demonstrate that human peripheral blood NK cells express nuclear oligomerization domain 2 and respond to MDP. NK cells naturally internalize MDP leading to direct cell activation, including signaling through NFB: characterized by p50/p65 heterodimers at early stimulations times and sustained activation of p50 homodimers. Moreover, MDP synergizes with IFN- and IL-12 to activate NK cells and stimulate IFN- secretion, suggesting a role for accessory cells in induction of an optimal NK cell response. Although IL-12 costimulation leads to a greater IFN- response by NK cells, higher levels of CD69 in response to MDP are induced in the presence of IFN-, suggesting that different pathogen-induced cytokine profiles will affect downstream NK cell responses. In contrast, MDP alone or in combination with either IFN- or IL-12 only poorly increases NK cell cytotoxicity. In summary, this report identifies MDP as a bacterial pathogen associated molecular pattern that activates human NK cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Clair Gardiner, School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. E-mail address: clair.gardiner{at}tcd.ie

² Abbreviations used in this paper: Nod, Nuclear oligomerization domain; MDP, muramyl dipeptide; PAMP, pathogen associated molecular pattern; gDNA, genomic DNA.