CEACAM engagement by human pathogens enhances cell adhesion and counteracts bacteria-induced detachment of epithelial cells.
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.
Muenzner
Petra
P
Zentrum für Infektionsforschung, Universität Würzburg, 97070 Würzburg, Germany.
Rohde
Manfred
M
Kneitz
Susanne
S
Hauck
Christof R
CR
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D000071063:Endoglin; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity*; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C064206:ENG protein, human; D000071063:Endoglin; D039001:Integrin alpha Chains; D019012:Integrin beta1; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; C090348:Opa protein, Neisseria