Interaction of Ipa proteins of Shigella flexneri with alpha5beta1 integrin promotes entry of the bacteria into mammalian cells.

Abstract

SummaryShigella is a genus of highly adapted bacterial pathogens that cause bacillary dysentery in humans.Bacteria reaching the colon invade intestinal epithehal cells by a process of bacterial-directed endocytosis mediated by the Ipa proteins: IpaB, IpaC, and IpaD of Shigella. The invasion of epithelial cells is thought to be a receptor-mediated phenomenon, although the cellular components of the host that interact with the Ipa proteins have not yet been identified. We report here that in a Shigellaflexneri invasive system and Chinese hamster ovary (CHO) cell monolayers, the Ipa proteins were capable of interacting directly with oL5131 integrin. The invasive capacity of S. flexneri for CHO cells increased as levels of cx5131 integrin were elevated. When CHO cells were infected with S. flexneri, the tyrosine phosphorylation both ofpp 125 F~, an integrin-regulated 125 K focal adhesion kinase, and of paxillin was stimulated. In contrast, an isogenic strain of S. flexneri that was defective in invasion owing to a mutation in its spa32 gene failed to induce such phosphorylation. Under in vitro and in vivo conditions, the released IpaB, IpaC, and IpaD proteins bound to ot5[~ 1 integrin in a manner different from that of soluble fibronectin but similar to that of the tissue form of fibronectin. At the site of attachment of S. flexneri to CHO cells, ot5131 integrin converged with polymerization of actin. These data thus suggest that the capacity oflpa proteins to interact with o~5151 integrin may be an important Shigella factor in triggering the reorganization of actin cytoskeletons.

Reconstituted Human Polyclonal Plasma-derived Secretory-like IgM and IgA Maintain the Barrier Function of Epithelial Cells Infected with an Enteropathogen

“…However, in vivo, the presence of bound SC is essential for the stability and anchoring of the molecule at mucosal surfaces (3). Furthermore, in addition to interfering with bacterial targeting of epithelial cells via carbohydrates abundantly found on its surface (44), SC associated with pIgA and IgM appears to intervene negatively in the secretion of S. flexneri virulence factors crucial for the infection of epithelial cells (45,46). These results suggest the unexpected role of polyclonal SIgA and SIgM mostly in altering bacterial metabolism, which adds to recognized mechanisms of protection effective at the level of the mucosal epithelium.…”

BAFF synthesis by rheumatoid synoviocytes is positively controlled by α5β1 integrin stimulation and is negatively regulated by tumor necrosis factor α and toll‐like receptor ligands

“…FLS express various integrins, and in this study, we also explored the ultimate implication of ␣5␤1 integrin, a well-known receptor of several bacterial PAMPs, in BAFF synthesis (26)(27)(28). Protein I/II, an adhesin derived from viridans streptococci, is an established ␣5␤1 integrin ligand that induces the release of classic proinflammatory cytokines, such as IL-6 and IL-8, by FLS (18).…”

CD44 binds to the Shigella IpaB protein and participates in bacterial invasion of epithelial cells

“…It has been proposed that insertion of the IpaB±C complex into target cell membranes could occur as a two-step process, implicating at ®rst secretion of the complex in the extracellular medium (Hueck, 1998). Alternatively, the extracellular form of this complex may participate in the entry process by establishing a link between the bacterial surface and cell receptors, such as b1 integrins, and transducing signals that participate in cytoskeletal reorganization at the site of bacterial entry (Watarai et al, 1996). Because it is becoming clear that that actin polymerization and ®lo-podia formation induced by Shigella during entry requires the presentation of the IpaC carboxy-terminus in the cell cytosol and, thus, insertion of the IpaB±C complex in the cell membrane, the signi®-cance of the interaction between this complex and cell receptors was investigated further in this study.…”

“…Also, a recombinant form of the C3 exoenzyme that speci®cally inhibits Rho, a small GTPase involved in the formation of stress ®bres and focal adhesions (Nobes and Hall, 1995), inhibits Shigella entry into epithelial cells (Adam et al, 1996;Mounier et al, 1999). Association of an IpaB±C±D complex with the a5b1 integrin was proposed as a possible mechanism for the induction of Shigella entry after signalling via b1 integrins (Watarai et al, 1996). However, the role of the interaction between Shigella effectors of entry and cell surface receptors, such as b1 integrins, remains unclear.…”