scholarly journals Neisseria gonorrhoeae Kills Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 (CD66a)-Expressing Human B Cells and Inhibits Antibody Production

2005 ◽  
Vol 73 (7) ◽  
pp. 4171-4179 ◽  
Author(s):  
Milica Pantelic ◽  
Young-June Kim ◽  
Silvia Bolland ◽  
Ines Chen ◽  
John Shively ◽  
...  
Keyword(s):  
Cell Death ◽  
B Cells ◽  
Neisseria Gonorrhoeae ◽  
Carcinoembryonic Antigen ◽  
Adhesion Molecule ◽  
Antibody Production ◽  
Cellular Adhesion ◽  
Cell Death Pathway ◽  
Human B Cells ◽  
Cellular Adhesion Molecule

ABSTRACT Neisseria gonorrhoeae cells (gonococci [GC]), the etiological agents for gonorrhea, can cause repeated infections. During and after gonococcal infection, local and systemic antigonococcal antibody levels are low. These clinical data indicate the possibility that GC may suppress immune responses during infection. Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1 or CD66a), a receptor for GC opacity (Opa) proteins, was shown to mediate inhibitory signals. In the present study, human B cells were activated by interleukin-2 to express CEACAM1 and then stimulated to secrete antibodies and simultaneously coincubated with Opa− and OpaI GC of strain MS11. Our results show that this OpaI GC has the ability to inhibit antibody production. The interaction of GC and CEACAM1 with human peripheral B cells also results in induction of cell death. The same findings were observed in DT40 B cells. This CEACAM1-promoted cell death pathway does not involve the inhibitory signals or the tyrosine phosphatases SHP-1 and SHP-2 but depends on Bruton's tyrosine kinase in DT40 cells. Our results suggest that Neisseria gonorrhoeae possesses the ability to suppress antibody production by killing CEACAM1-expressing B cells.

scholarly journals Engulfment of Neisseria gonorrhoeae: Revealing Distinct Processes of Bacterial Entry by Individual Carcinoembryonic Antigen-Related Cellular Adhesion Molecule Family Receptors

2004 ◽  
Vol 72 (5) ◽  
pp. 2742-2752 ◽  
Author(s):  
Shannon E. McCaw ◽  
Edward H. Liao ◽  
Scott D. Gray-Owen
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Carcinoembryonic Antigen ◽  
Adhesion Molecule ◽  
Cellular Response ◽  
Cellular Adhesion ◽  
Target Cells ◽  
Phase Variable ◽  
Cellular Adhesion Molecule ◽  
Variable Nature ◽  
Protein Variants

ABSTRACT Individual Neisseria gonorrhoeae colony opacity-associated (Opa) protein variants can bind up to four different carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) receptors. Most human cells encountered by gonococci express a combination of CEACAM receptors, thereby complicating the elucidation of intracellular signaling pathways triggered by individual receptors. Here, we compare the process of bacterial engulfment by a panel of stably transfected HeLa epithelial cell lines expressing each CEACAM receptor in isolation. CEACAM1 and CEACAM3 each contain proteinaceous transmembrane and cytoplasmic domains; however, the processes of neisserial uptake mediated by these receptors differ with respect to their susceptibilities to both tyrosine kinase inhibitors and the actin microfilament-disrupting agent cytochalasin D. Neisserial uptake mediated by glycosylphosphatidylinositol (GPI)-anchored CEACAM5 and CEACAM6 was not significantly affected by any of a broad spectrum of inhibitors tested. However, cleavage of the GPI anchor by phosphatidylinositol-specific phospholipase C reduced bacterial uptake by HeLa cells expressing CEACAM5, consistent with a single zipper-like mechanism of uptake mediated by this receptor. Regardless of the CEACAM receptor expressed, internalized gonococci were effectively killed by a microtubule-dependent process that required acidification of the bacterium-containing phagosome. Given the phase-variable nature of neisserial Opa proteins, these results indicate that the mechanism of bacterial engulfment and the cellular response to gonococcal infection depend on both the receptor specificities of the neisserial Opa protein variants expressed and the spectrum of CEACAM receptors present on target cells, each of which determines the combination of receptors ultimately engaged.

Carcinoembryonic Antigen-Related Cellular Adhesion Molecule 1 Isoforms Alternatively Inhibit and Costimulate Human T Cell Function

2004 ◽  
Vol 172 (6) ◽  
pp. 3535-3543 ◽  
Author(s):  
Daohong Chen ◽  
Hideki Iijima ◽  
Takashi Nagaishi ◽  
Atsushi Nakajima ◽  
Sara Russell ◽  
...  
Keyword(s):  
T Cell ◽  
Carcinoembryonic Antigen ◽  
Adhesion Molecule ◽  
Cell Function ◽  
Cellular Adhesion ◽  
T Cell Function ◽  
Human T Cell ◽  
Cellular Adhesion Molecule

scholarly journals Neonatally Induced Inactivation of the Vascular Cell Adhesion Molecule 1 Gene Impairs B Cell Localization and T Cell–Dependent Humoral Immune Response

2001 ◽  
Vol 193 (6) ◽  
pp. 755-768 ◽  
Author(s):  
Christoph E. Leuker ◽  
Mark Labow ◽  
Werner Müller ◽  
Norbert Wagner
Keyword(s):  
Immune Response ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Adhesion Molecule ◽  
Humoral Immune Response ◽  
Cellular Adhesion ◽  
Humoral Immune ◽  
Cell Localization ◽  
Cellular Adhesion Molecule

Vascular cellular adhesion molecule (VCAM)-1 is a membrane-bound cellular adhesion molecule that mediates adhesive interactions between hematopoietic progenitor cells and stromal cells in the bone marrow (BM) and between leukocytes and endothelial as well as dendritic cells. Since VCAM-1–deficient mice die embryonically, conditional VCAM-1 mutant mice were generated to analyze the in vivo function of this adhesion molecule. Here we show that interferon-induced Cre-loxP–mediated deletion of the VCAM-1 gene after birth efficiently ablates expression of VCAM-1 in most tissues like, for example, BM, lymphoid organs, and lung, but not in brain. Induced VCAM-1 deficiency leads to a reduction of immature B cells in the BM and to an increase of these cells in peripheral blood but not in lymphoid organs. Mature recirculating B cells are reduced in the BM. In a migration assay, the number of mature B cells that appears in the BM after intravenous injection is decreased. In addition, the humoral immune response to a T cell–dependent antigen is impaired. VCAM-1 serves an important role for B cell localization and the T cell–dependent humoral immune response.

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