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CEACAM engagement by human pathogens enhances cell adhesion and counteracts bacteria-induced detachment of epithelial cells.

Muenzner P, Rohde M, Kneitz S, Hauck CR - J. Cell Biol. (2005)

Bottom Line: Blockage of CD105 expression by antisense oligonucleotides abolished infection-induced cell adhesion.The CD105-mediated increase in cell adhesion was dependent on the presence and function of integrin beta1.CD105 expression did not elevate cellular integrin levels but caused a dramatic increase in the ECM-binding capacity of the cells, suggesting that CD105 affects integrin activity.

View Article: PubMed Central - PubMed

Affiliation: Zentrum für Infektionsforschung, Universität Würzburg, 97070 Würzburg, Germany.

ABSTRACT
Exfoliation, which is the detachment of infected epithelial cells, is an innate defense mechanism to prevent bacterial colonization. Indeed, infection with Neisseria gonorrhoeae induced epithelial detachment from an extracellular matrix (ECM) substrate in vitro. Surprisingly, variants of N. gonorrhoeae that bind to human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) failed to induce detachment and, instead, promoted enhanced host cell adhesion to the ECM. Microarray analysis revealed that CEACAM engagement by several human pathogens triggers expression of CD105. Blockage of CD105 expression by antisense oligonucleotides abolished infection-induced cell adhesion. The expression of full-length CD105 promoted cell adhesion to the ECM and was sufficient to prevent infection-induced detachment. The CD105-mediated increase in cell adhesion was dependent on the presence and function of integrin beta1. CD105 expression did not elevate cellular integrin levels but caused a dramatic increase in the ECM-binding capacity of the cells, suggesting that CD105 affects integrin activity. The exploitation of CEACAMs to trigger CD105 expression and to counteract infection-induced cell detachment represents an intriguing adaptation of pathogens that are specialized to colonize the human mucosa.

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CD105 is sufficient to promote cell adhesion and to prevent bacteria-induced cell detachment. (A) 293T cells were transfected as indicated and were infected or left uninfected for 8 h with OpaCEA-expressing N. gonorrhoeae. Cells were used in adhesion assays. Bottom panel depicts Western blots of whole cell lysates (WCL) from transfected cells. (B) 293T cells transfected with empty vector (pcDNA), CEACAM1, CEACAM6, or CD105-GFP were infected for 14 h with the indicated bacterial strains. Cells were used in a detachment assay before microphotographs were taken. (C) 293T cells were transfected with empty vector (pcDNA), CD105 WT, CD105 ΔCT, or CD105 Δ35 and were used in adhesion assays. Error bars represent means ± SD of five samples (A) or wells (C). (D) 293T cells transfected as in C were seeded in 24-well plates, and photographs were taken before infection. Cells were then infected for 14 h with the indicated bacterial strains and were used in a detachment assay before remaining cells were photographed.
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fig6: CD105 is sufficient to promote cell adhesion and to prevent bacteria-induced cell detachment. (A) 293T cells were transfected as indicated and were infected or left uninfected for 8 h with OpaCEA-expressing N. gonorrhoeae. Cells were used in adhesion assays. Bottom panel depicts Western blots of whole cell lysates (WCL) from transfected cells. (B) 293T cells transfected with empty vector (pcDNA), CEACAM1, CEACAM6, or CD105-GFP were infected for 14 h with the indicated bacterial strains. Cells were used in a detachment assay before microphotographs were taken. (C) 293T cells were transfected with empty vector (pcDNA), CD105 WT, CD105 ΔCT, or CD105 Δ35 and were used in adhesion assays. Error bars represent means ± SD of five samples (A) or wells (C). (D) 293T cells transfected as in C were seeded in 24-well plates, and photographs were taken before infection. Cells were then infected for 14 h with the indicated bacterial strains and were used in a detachment assay before remaining cells were photographed.

Mentions: To investigate whether enhanced expression of CD105 is sufficient to promote epithelial cell adhesion, 293T cells were transfected with cDNA encoding full-length human CD105, and their adhesive properties were compared with CEACAM1-transfected cells before and after infection with OpaCEA gonococci. Strikingly, CD105 overexpression in 293T cells in the absence of bacterial infection led to increases in cell adhesion similar to those observed after infection of CEACAM-positive cells with OpaCEA gonococci (Fig. 6 A). CD105 overexpression enhanced cell adhesion to collagen and also increased cell adhesion to gelatine, matrigel, and, to a lesser extent, fibronectin (Fig. S5 A, available at http://www.jcb.org/cgi/content/full/jcb.200412151/DC1). 293T cells overexpressing CD105 were resistant to bacteria-induced detachment even after prolonged infection with both CEACAM-binding and nonbinding microorganisms, which is consistent with a role for CD105 in the prevention of epithelial cell detachment (Fig. 6 B). Altogether, these results demonstrated that enhanced surface expression of CD105 is sufficient to mediate increased cell adhesion to ECM substrates and to prevent epithelial cell detachment after bacterial engagement of CEACAMs.


CEACAM engagement by human pathogens enhances cell adhesion and counteracts bacteria-induced detachment of epithelial cells.

Muenzner P, Rohde M, Kneitz S, Hauck CR - J. Cell Biol. (2005)

CD105 is sufficient to promote cell adhesion and to prevent bacteria-induced cell detachment. (A) 293T cells were transfected as indicated and were infected or left uninfected for 8 h with OpaCEA-expressing N. gonorrhoeae. Cells were used in adhesion assays. Bottom panel depicts Western blots of whole cell lysates (WCL) from transfected cells. (B) 293T cells transfected with empty vector (pcDNA), CEACAM1, CEACAM6, or CD105-GFP were infected for 14 h with the indicated bacterial strains. Cells were used in a detachment assay before microphotographs were taken. (C) 293T cells were transfected with empty vector (pcDNA), CD105 WT, CD105 ΔCT, or CD105 Δ35 and were used in adhesion assays. Error bars represent means ± SD of five samples (A) or wells (C). (D) 293T cells transfected as in C were seeded in 24-well plates, and photographs were taken before infection. Cells were then infected for 14 h with the indicated bacterial strains and were used in a detachment assay before remaining cells were photographed.
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fig6: CD105 is sufficient to promote cell adhesion and to prevent bacteria-induced cell detachment. (A) 293T cells were transfected as indicated and were infected or left uninfected for 8 h with OpaCEA-expressing N. gonorrhoeae. Cells were used in adhesion assays. Bottom panel depicts Western blots of whole cell lysates (WCL) from transfected cells. (B) 293T cells transfected with empty vector (pcDNA), CEACAM1, CEACAM6, or CD105-GFP were infected for 14 h with the indicated bacterial strains. Cells were used in a detachment assay before microphotographs were taken. (C) 293T cells were transfected with empty vector (pcDNA), CD105 WT, CD105 ΔCT, or CD105 Δ35 and were used in adhesion assays. Error bars represent means ± SD of five samples (A) or wells (C). (D) 293T cells transfected as in C were seeded in 24-well plates, and photographs were taken before infection. Cells were then infected for 14 h with the indicated bacterial strains and were used in a detachment assay before remaining cells were photographed.
Mentions: To investigate whether enhanced expression of CD105 is sufficient to promote epithelial cell adhesion, 293T cells were transfected with cDNA encoding full-length human CD105, and their adhesive properties were compared with CEACAM1-transfected cells before and after infection with OpaCEA gonococci. Strikingly, CD105 overexpression in 293T cells in the absence of bacterial infection led to increases in cell adhesion similar to those observed after infection of CEACAM-positive cells with OpaCEA gonococci (Fig. 6 A). CD105 overexpression enhanced cell adhesion to collagen and also increased cell adhesion to gelatine, matrigel, and, to a lesser extent, fibronectin (Fig. S5 A, available at http://www.jcb.org/cgi/content/full/jcb.200412151/DC1). 293T cells overexpressing CD105 were resistant to bacteria-induced detachment even after prolonged infection with both CEACAM-binding and nonbinding microorganisms, which is consistent with a role for CD105 in the prevention of epithelial cell detachment (Fig. 6 B). Altogether, these results demonstrated that enhanced surface expression of CD105 is sufficient to mediate increased cell adhesion to ECM substrates and to prevent epithelial cell detachment after bacterial engagement of CEACAMs.

Bottom Line: Blockage of CD105 expression by antisense oligonucleotides abolished infection-induced cell adhesion.The CD105-mediated increase in cell adhesion was dependent on the presence and function of integrin beta1.CD105 expression did not elevate cellular integrin levels but caused a dramatic increase in the ECM-binding capacity of the cells, suggesting that CD105 affects integrin activity.

View Article: PubMed Central - PubMed

Affiliation: Zentrum für Infektionsforschung, Universität Würzburg, 97070 Würzburg, Germany.

ABSTRACT
Exfoliation, which is the detachment of infected epithelial cells, is an innate defense mechanism to prevent bacterial colonization. Indeed, infection with Neisseria gonorrhoeae induced epithelial detachment from an extracellular matrix (ECM) substrate in vitro. Surprisingly, variants of N. gonorrhoeae that bind to human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) failed to induce detachment and, instead, promoted enhanced host cell adhesion to the ECM. Microarray analysis revealed that CEACAM engagement by several human pathogens triggers expression of CD105. Blockage of CD105 expression by antisense oligonucleotides abolished infection-induced cell adhesion. The expression of full-length CD105 promoted cell adhesion to the ECM and was sufficient to prevent infection-induced detachment. The CD105-mediated increase in cell adhesion was dependent on the presence and function of integrin beta1. CD105 expression did not elevate cellular integrin levels but caused a dramatic increase in the ECM-binding capacity of the cells, suggesting that CD105 affects integrin activity. The exploitation of CEACAMs to trigger CD105 expression and to counteract infection-induced cell detachment represents an intriguing adaptation of pathogens that are specialized to colonize the human mucosa.

Show MeSH
Related in: MedlinePlus