The Journal of Experimental Medicine
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Published online January 7, 2008
doi:10.1084/jem.20071164
The Journal of Experimental Medicine, Vol. 205, No. 1, 169-181
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Ip et al.
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ARTICLE

 Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome

W.K. Eddie Ip1, Kazue Takahashi1, Kathryn J. Moore2, Lynda M. Stuart1,3, and R. Alan B. Ezekowitz1

1 Laboratory of Developmental Immunology, Department of Pediatrics and 2 Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114
3 Center for Inflammation Research, University of Edinburgh, Edinburgh EH8 9AG, Scotland, UK

CORRESPONDENCE W.K. Eddie Ip: eddie_ip{at}hms.harvard.edu OR Lynda M. Stuart lstuart{at}partners.org

Innate immunity is the first-line defense against pathogens and relies on phagocytes, soluble components, and cell-surface and cytosolic pattern recognition receptors. Despite using hard-wired receptors and signaling pathways, the innate immune response demonstrates surprising specificity to different pathogens. We determined how combinatorial use of innate immune defense mechanisms defines the response. We describe a novel cooperation between a soluble component of the innate immune system, the mannose-binding lectin, and Toll-like receptor 2 that both specifies and amplifies the host response to Staphylococcus aureus. Furthermore, we demonstrate that this cooperation occurs within the phagosome, emphasizing the importance of engulfment in providing the appropriate cellular environment to facilitate the synergy between these defense pathways.

Abbreviations used: LBP, LPS-binding protein; LTA, lIpoteichoic acid; MBL, mannose-binding lectin; MFI, mean fluorescence intensity; MOI, multiplicity of infection; PGN, peptidoglycan; SP, surfactant protein; TAMRA, tetramethyl-6-carboxyrhodamine; TLR, Toll-like receptor.

L.M. Stuart and R.A.B. Ezekowitz contributed equally to this work.

R.A.B. Ezekowitz's present address is Merck Research Laboratories, Rahway, NJ 07065.


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