Cell adhesion receptors - signaling capacity and exploitation by bacterial pathogens

Abstract

Cell adhesion receptors play an essential role in multicellular organisms by mediating the direct association of cells with each other and with proteins of the extracellular matrix. Members of different protein families such as integrins, cadherins, immunoglobulin superfamily cell adhesion molecules (IgCAMs), selectins, and syndecans not only support the structural integrity of cells and tissues, but also contribute to the transduction of signals. Interestingly, several of these molecules are exploited by bacterial pathogens to establish tight contact with eukaryotic cells. Using the example of integrins, cadherins, and IgCAMs, this review illustrates the signaling capacity of cell adhesion receptors and highlights a number of bacterial adhesins that are known to engage these receptors. Where applicable, the role of the receptor-adhesin interaction in the course of the infection is discussed.

Temporal upregulation of host surface receptors provides a window of opportunity for bacterial adhesion and disease

“…integrins, cadherins), and platelet-activating factor receptor (PAFR), which upon stimulation by certain environmental and/or immunogenic insults, undergo transient upregulation. This enhances bacterial adherence and subsequent tissue invasion [3][4][5].…”

“…In addition to ECM components, cell adhesion molecules, including integrins, cadherins, selectins and members of the immunoglobulin superfamily of cell adhesion molecules (IgCAMs), are also involved in bacterial adhesion [4,12]. Integrins are heterodimeric (composed of two subunits, a and b) transmembrane glycoproteins that attach cells to ECM proteins of the basement membrane or to ligands on other cells [13,14].…”

“…Several bacteria bind directly to integrins whereas others engage them via ECM proteins, such as fibronectin and collagen. Bacterial-integrin binding can trigger host intracellular signalling leading to actin cytoskeleton remodelling and subsequent bacterial invasion [4].…”

“…IgCAMs, including the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) and intercellular cell adhesion molecule 1 (ICAM-1), constitute the other major class of host cell receptors utilized by bacterial adhesion systems [4]. The CEACAM family is a group of highly glycosylated intercellular adhesion molecules involved in signalling events that mediate key processes including cell adhesion, proliferation, differentiation and tumour suppression [15].…”

Quantification of bacterial invasion into adherent cells by flow cytometry

“…In some instances, bacteria inject proteins, e.g., via type III secretion systems, to directly modulate intracellular regulators of actin dynamics such as the Rho family GTPases (Galan and Zhou, 2000;Tran Van Nhieu et al, 2000). In other cases, the bacteria use an indirect route by engaging cell surface receptors coupled to the cytoskeleton including integrins, cadherins or immunoglobulin-related cell adhesion molecules (Hauck, 2002). For example, S. flexneri as well as S. aureus are able to connect to cell surface integrins to trigger actin-dependent internalization (Watarai et al, 1996;Sinha et al, 1999;Agerer et al, 2005).…”