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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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Related in: MedlinePlus

Diverse CEACAM-binding human-specific microorganisms trigger enhanced cell adhesion. 293T cells were transfected with CEACAM1 (black bars) or CD105-GFP (white bars). Cells were left uninfected or were infected for 8 h with OpaCEA N. gonorrhoeae (Ngo OpaCEA), Opa-expressing N. meningitidis (Nme OpaCEA), H. influenzae (H. inf.), M. catarrhalis (M. cat.), or nonopaque N. gonorrhoeae (Ngo Opa−) and were used in adhesion assays. Error bars represent means ± SD of five wells.
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fig9: Diverse CEACAM-binding human-specific microorganisms trigger enhanced cell adhesion. 293T cells were transfected with CEACAM1 (black bars) or CD105-GFP (white bars). Cells were left uninfected or were infected for 8 h with OpaCEA N. gonorrhoeae (Ngo OpaCEA), Opa-expressing N. meningitidis (Nme OpaCEA), H. influenzae (H. inf.), M. catarrhalis (M. cat.), or nonopaque N. gonorrhoeae (Ngo Opa−) and were used in adhesion assays. Error bars represent means ± SD of five wells.

Mentions: Up-regulation of CD105 via CEACAM engagement could be a general mechanism that is used by multiple human-specific pathogens to prevent epithelial cell detachment. To analyze whether other CEACAM-binding bacteria are able to trigger enhanced cell adhesion to collagen, 293T cells were transfected with CEACAM1 and were infected with a variety of gram-negative CEACAM-binding bacteria, including N. meningitidis, H. influenzae, and M. catarrhalis. As a positive control, cells were transfected with human CD105. As observed previously, the expression of human CD105 was sufficient to enhance 293T cell adhesion to collagen (Fig. 9). Plating of the infected cells onto collagen-coated surfaces again revealed a strong increase in cell adhesion in response to OpaCEA-expressing, but not to nonopaque, gonococci (Fig. 9). Importantly, all CEACAM-binding microorganisms were able to significantly induce cell adhesion to collagen, whereas an attachment to uncoated cell culture surface was unaltered (Fig. 9). Together, these results demonstrate that a variety of CEACAM-binding bacteria is able to trigger enhanced epithelial cell adhesion to ECM proteins and suggest that this might be a common strategy to facilitate the colonization of epithelial cell layers of their human host.


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)

Diverse CEACAM-binding human-specific microorganisms trigger enhanced cell adhesion. 293T cells were transfected with CEACAM1 (black bars) or CD105-GFP (white bars). Cells were left uninfected or were infected for 8 h with OpaCEA N. gonorrhoeae (Ngo OpaCEA), Opa-expressing N. meningitidis (Nme OpaCEA), H. influenzae (H. inf.), M. catarrhalis (M. cat.), or nonopaque N. gonorrhoeae (Ngo Opa−) and were used in adhesion assays. Error bars represent means ± SD of five wells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171332&req=5

fig9: Diverse CEACAM-binding human-specific microorganisms trigger enhanced cell adhesion. 293T cells were transfected with CEACAM1 (black bars) or CD105-GFP (white bars). Cells were left uninfected or were infected for 8 h with OpaCEA N. gonorrhoeae (Ngo OpaCEA), Opa-expressing N. meningitidis (Nme OpaCEA), H. influenzae (H. inf.), M. catarrhalis (M. cat.), or nonopaque N. gonorrhoeae (Ngo Opa−) and were used in adhesion assays. Error bars represent means ± SD of five wells.
Mentions: Up-regulation of CD105 via CEACAM engagement could be a general mechanism that is used by multiple human-specific pathogens to prevent epithelial cell detachment. To analyze whether other CEACAM-binding bacteria are able to trigger enhanced cell adhesion to collagen, 293T cells were transfected with CEACAM1 and were infected with a variety of gram-negative CEACAM-binding bacteria, including N. meningitidis, H. influenzae, and M. catarrhalis. As a positive control, cells were transfected with human CD105. As observed previously, the expression of human CD105 was sufficient to enhance 293T cell adhesion to collagen (Fig. 9). Plating of the infected cells onto collagen-coated surfaces again revealed a strong increase in cell adhesion in response to OpaCEA-expressing, but not to nonopaque, gonococci (Fig. 9). Importantly, all CEACAM-binding microorganisms were able to significantly induce cell adhesion to collagen, whereas an attachment to uncoated cell culture surface was unaltered (Fig. 9). Together, these results demonstrate that a variety of CEACAM-binding bacteria is able to trigger enhanced epithelial cell adhesion to ECM proteins and suggest that this might be a common strategy to facilitate the colonization of epithelial cell layers of their human host.

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