Engagement of integrins as a cellular route of invasion by bacterial pathogens

Scibelli, Antonio; Roperto, Sante; Manna, Laura; Pavone, Luigi Michele; Tafuri, Simona; Morte, Renata Della; Staiano, Norma

doi:10.1016/j.tvjl.2006.01.010

Cited by 48 publications

(38 citation statements)

References 87 publications

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“…The induction of autophagy involved the Yersinia adhesins invasin and YadA which cluster ␤ 1 integrins to gain access into eukaryotic cells (26,27,58). Many bacteria and viruses stimulate ␤ 1 integrins (75)(76)(77), and this is a first study demonstrating the induction of autophagy as a result of microbial ␤ 1 integrin activation. The activation of autophagy could be a general feature of ␤ 1 integrin-dependent phagocytosis.…”

Section: Discussionmentioning

confidence: 98%

“…This opens up new perspectives in studying the functions and consequences of integrin stimulation. Many bacteria and viruses activate host cells via integrin receptors (75)(76)(77). The sensing of microbes by ␤ 1 integrins may therefore be a general principle that serves to induce autophagy and to promote the elimination of extracellular pathogens.…”

Section: Discussionmentioning

confidence: 99%

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β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

Deuretzbacher

Czymmeck

Reimer

et al. 2009

The Journal of Immunology

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Autophagy is a central lysosomal degradation process that is essential for the maintenance of cellular homeostasis. Autophagy has furthermore emerged as integral part of the host immune response. Autophagic processes promote the separation and degradation of intracellular microorganisms which contributes to the development of innate and adaptive immunity. Some pathogenic microbes have therefore evolved mechanisms to evade or impede autophagy. We analyzed the effects of the enteropathogenic bacterium Yersinia enterocolitica on autophagy in macrophages. Yersiniae use a number of defined adhesins and secreted proteins to manipulate host immune responses. Our results showed that Y. enterocolitica defective in type III protein secretion efficiently activated autophagy in macrophages. Autophagy was mediated by the Yersinia adhesins invasin and YadA and particularly depended on the engagement of β1 integrin receptors. Several autophagy-related events followed β1 integrin-mediated engulfment of the bacteria including the formation of autophagosomes, processing of the marker protein LC3, redistribution of GFP-LC3 to bacteria-containing vacuoles, and the segregation of intracellular bacteria by autophagosomal compartments. These results provide direct evidence for the linkage of β1 integrin-mediated phagocytosis and autophagy induction. Multiple microbes signal through integrin receptors, and our results suggest a general principle by which the sensing of an extracellular microbe triggers autophagy. Owing to the importance of autophagy as host defense response, wild-type Y. enterocolitica suppressed autophagy by mobilizing type III protein secretion. The subversion of autophagy may be part of the Y. enterocolitica virulence strategy that supports bacterial survival when β1 integrin-dependent internalization and autophagy activation by macrophages are deleterious for the pathogen.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

Deuretzbacher

Czymmeck

Reimer

et al. 2009

The Journal of Immunology

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“…As a heterodimer, α3β1 integrin can bind a number of ECM components, including laminin, fibronectin, and collagen [66]. Recognition of ECM proteins allows many pathogens to interact indirectly with host integrin receptors [45]. FimH itself is able to bind the matrix-associated proteins laminin, fibronectin, and type IV collagens, which could in turn link UPEC with integrin receptors [32–34].…”

Section: Discussionmentioning

confidence: 99%

Integrin-Mediated Host Cell Invasion by Type 1–Piliated Uropathogenic Escherichia coli

et al. 2007

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Uropathogenic Escherichia coli (UPEC), the primary causative agent of urinary tract infections, typically express filamentous adhesive organelles called type 1 pili that mediate both bacterial attachment to and invasion of bladder urothelial cells. Several host proteins have previously been identified as receptors for type 1 pili, but none have been conclusively shown to promote UPEC entry into host bladder cells. Using overlay assays with FimH, the purified type 1 pilus adhesin, and mass spectroscopy, we have identified β1 and α3 integrins as key host receptors for UPEC. FimH recognizes N-linked oligosaccharides on these receptors, which are expressed throughout the urothelium. In a bladder cell culture system, β1 and α3 integrin receptors co-localize with invading type 1–piliated bacteria and F-actin. FimH-mediated bacterial invasion of host bladder cells is inhibited by β1 and α3 integrin–specific antibodies and by disruption of the β1 integrin gene in the GD25 fibroblast cell line. Phosphorylation site mutations within the cytoplasmic tail of β1 integrin that alter integrin signaling also variably affect UPEC entry into host cells, by either attenuating or boosting invasion frequencies. Furthermore, focal adhesion and Src family kinases, which propagate integrin-linked signaling and downstream cytoskeletal rearrangements, are shown to be required for FimH-dependent bacterial invasion of target host cells. Cumulatively, these results indicate that β1 and α3 integrins are functionally important receptors for type 1 pili–expressing bacteria within the urinary tract and possibly at other sites within the host.

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“…By invading the host body, adhesion is one of the first steps for several of these pathogens, which interact with host proteins that include, for example, extracellular matrix (ECM) proteins, integrins, cadherins and lectins. By binding to these proteins, pathogens may exploit host signaling pathways like activation of Src-family kinases (SFKs), MAPKs, Rho GTPases and others, promoting their movement within and across epithelia and endothelia, or even manipulating host defenses, leading to the success of infection [5,22]. As some of these receptors and signaling molecules may be clustered into cholesterol-and sphingolipid-enriched cell surface domains termed membrane rafts [11,23], we evaluated whether membrane rafts of epithelial cells are involved in the adhesion of yeast forms of P. brasiliensis.…”

Section: Discussionmentioning

confidence: 99%

Interaction of epithelial cell membrane rafts with Paracoccidioides brasiliensis leads to fungal adhesion and Src-family kinase activation

Maza

Straus

Toledo

et al. 2008

Microbes and Infection

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Engagement of integrins as a cellular route of invasion by bacterial pathogens

Cited by 48 publications

References 87 publications

β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

β1 Integrin-Dependent Engulfment of Yersinia enterocolitica by Macrophages Is Coupled to the Activation of Autophagy and Suppressed by Type III Protein Secretion

Integrin-Mediated Host Cell Invasion by Type 1–Piliated Uropathogenic Escherichia coli

Interaction of epithelial cell membrane rafts with Paracoccidioides brasiliensis leads to fungal adhesion and Src-family kinase activation

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