I-domain-containing integrins serve as pilus receptors for Neisseria gonorrhoeae adherence to human epithelial cells

Abstract

Two pilus receptors are identified for the pathogenic Neisseria, CD46 and complement receptor 3. An intimate association between the asialoglycoprotein receptor and gonococcal lipooligosaccharide mediates invasion of primary, male urethral epithelial cells (UECs); however, studies to identify pilus receptors on these cells have not been performed. Based on our previous studies we reasoned that the I-domain-containing (IDC), α1- and α2-integrins might serve as pilus receptors on UECs and on urethral tissue. Confocal microscopy revealed colocalization of plius with α1 and α2 integrins on UECs and tissue. We found that recombinant I-domain and antibodies directed against the α1- and α2-integrins inhibited gonococcal association with UECs and with immortal cell lines of variable origin. Gonococcus-integrin colocallization occurred at early time points post infection, but this interaction dissociated with extended infection. Similarly, Western Blot analyses revealed that gonococcal pilin coimmunoprecipitates with α1- and α2-integrins. However, studies performed in parallel and that were designed to capture CD46-pilus immune complexes indicated that a CD46-pilus interaction did not occur. Collectively, these data suggest that while CD46 might be able to bind gonococcal pilus, IDC integrins are preferentially used as the initial docking site for gonococci on UECs, on urethral tissue and on some immortal cell lines. © 2005 Blackwell Publishing Ltd.