The Journal of Experimental Medicine
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Published 5 January 2004. doi:10.1084/jem.20030204
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 1, 35-46
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Granulocyte CEACAM3 Is a Phagocytic Receptor of the Innate Immune System that Mediates Recognition and Elimination of Human-specific Pathogens

Tim Schmitter, Franziska Agerer, Lisa Peterson, Petra Münzner and Christof R. Hauck

Zentrum für Infektionsforschung, Universität Würzburg, 97070 Würzburg, Germany

Address correspondence to Christof R. Hauck, Zentrum für Infektionsforschung, Universität Würzburg, Röntgenring 11, 97070 Würzburg, Germany. Phone: 49-0-931-312137; Fax: 49-0-931-312578; email: christof.hauck{at}mail.uni-wuerzburg.de

Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are used by several human pathogens to anchor themselves to or invade host cells. Interestingly, human granulocytes express a specific isoform, CEACAM3, that participates together with CEACAM1 and CEACAM6 in the recognition of CEACAM-binding microorganisms. Here we show that CEACAM3 can direct efficient, opsonin-independent phagocytosis of CEACAM-binding Neisseria, Moraxella, and Haemophilus species. CEACAM3- but not CEACAM6-mediated uptake is blocked by dominant-negative versions of the small GTPase Rac. Moreover, CEACAM3 engagement triggers membrane recruitment and increased GTP loading of Rac that are not observed upon bacterial binding to CEACAM6. Internalization and Rac stimulation are also inhibited by compromising the integrity of an immunoreceptor tyrosine-based activation motif (ITAM)–like sequence in the cytoplasmic tail of CEACAM3 or by interference with Src family protein tyrosine kinases that phosphorylate CEACAM3. In contrast to interfering with CEACAM6, blockage of CEACAM3-mediated events reduces the ability of primary human granulocytes to internalize and eliminate CEACAM-binding bacteria, indicating an important role of CEACAM3 in the control of human-specific pathogens by the innate immune system.

Key Words: Neisseria gonorrhoeae • Opa protein • Haemophilus influenzae • Moraxella catarrhalis • innate immunity

Abbreviations used in this paper: CEACAM, carcinoembryonic antigen-related cell adhesion molecule; ITAM, immunoreceptor tyrosine-based activation motif; PI-3K, phosphatidylinositol 3'-kinase; PTK, protein tyrosine kinase.

The online version of this article includes supplemental material.


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