Uropathogenic Escherichia coli as a model of host–parasite interaction

Svanborg, Catharina; Bergsten, Göran; Fischer, Hans; Godaly, Gabriela; Gustafsson, Mattias C. U.; Karpman, Diana; Lundstedt, Ann-Charlotte; Ragnarsdóttir, Bryndís; Svensson, Majlis; Wullt, Björn

doi:10.1016/j.mib.2005.12.012

Cited by 99 publications

(92 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…E. coli is the primary cause of urinary tract infections in humans (24). The antibacterial defense of the urinary tract is highly dependent on innate immunity where PMNs are crucial players (25). Arguably, Ag43-mediated uptake and survival in PMNs could play an important role in this type of infections.…”

Section: Resultsmentioning

confidence: 99%

Biological Trojan Horse: Antigen 43 Provides Specific Bacterial Uptake and Survival in Human Neutrophils

et al. 2007

View full text Add to dashboard Cite

Escherichia coli is a versatile pathogen causing millions of infections in humans every year. This bacterium can form multicellular aggregates when it expresses a self-associating protein, antigen 43 (Ag43), on its surface. We have discovered that Ag43-expressing E. coli cells are efficiently taken up by human defense cells, polymorphonuclear neutrophils (PMNs), in an opsonin-independent manner. Surprisingly, the phagocytosed bacteria were not immediately killed but resided as tight aggregates within the PMNs. Our observations indicate that Ag43-mediated uptake and survival in PMNs constitute a mechanism to subvert one of the primary defense mechanisms of the human body.

show abstract

Section: Resultsmentioning

confidence: 99%

Biological Trojan Horse: Antigen 43 Provides Specific Bacterial Uptake and Survival in Human Neutrophils

et al. 2007

View full text Add to dashboard Cite

show abstract

“…UPEC expresses multiple adhesins and virulence factors that provoke inflammation and enable bacterial colonization of the bladder as the first step in UTI pathogenesis (2)(3)(4)(5). UPEC may also suppress innate immune responses (6)(7)(8).…”

mentioning

confidence: 99%

Innate Transcriptional Networks Activated in Bladder in Response to Uropathogenic Escherichia coli Drive Diverse Biological Pathways and Rapid Synthesis of IL-10 for Defense against Bacterial Urinary Tract Infection

Duell

Carey

Tan

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Early transcriptional activation events that occur in bladder immediately following bacterial urinary tract infection (UTI) are not well defined. In this study, we describe the whole bladder transcriptome of uropathogenic Escherichia coli (UPEC) cystitis in mice using genome-wide expression profiling to define the transcriptome of innate immune activation stemming from UPEC colonization of the bladder. Bladder RNA from female C57BL/6 mice, analyzed using 1.0 ST-Affymetrix microarrays, revealed extensive activation of diverse sets of innate immune response genes, including those that encode multiple IL-family members, receptors, metabolic regulators, MAPK activators, and lymphocyte signaling molecules. These were among 1564 genes differentially regulated at 2 h postinfection, highlighting a rapid and broad innate immune response to bladder colonization. Integrative systems-level analyses using InnateDB (http://www.innatedb.com) bioinformatics and ingenuity pathway analysis identified multiple distinct biological pathways in the bladder transcriptome with extensive involvement of lymphocyte signaling, cell cycle alterations, cytoskeletal, and metabolic changes. A key regulator of IL activity identified in the transcriptome was IL-10, which was analyzed functionally to reveal marked exacerbation of cystitis in IL-10–deficient mice. Studies of clinical UTI revealed significantly elevated urinary IL-10 in patients with UPEC cystitis, indicating a role for IL-10 in the innate response to human UTI. The whole bladder transcriptome presented in this work provides new insight into the diversity of innate factors that determine UTI on a genome-wide scale and will be valuable for further data mining. Identification of protective roles for other elements in the transcriptome will provide critical new insight into the complex cascade of events that underpin UTI.

show abstract

“…Innate immunity is the first line of defense in the urinary tract and triggered by uropathogenic bacteria through activation of Toll-like receptors (TLRs) located on the uroepithelial cell surface (32). Lipopolysaccharide (LPS) is an established ligand for Toll-like receptor 4 (TLR4), but associated coeffector proteins, such as CD14 and MD2, are needed for LPS-induced stimulation of TLR4 (4,27).…”

mentioning

confidence: 99%

“…Once activated, the uroepithelial cells play a central role in the host proinflammatory response through production of chemotactic substances, such as interleukin 6 (IL-6) and IL-8. Several lines of evidence demonstrate that IL-8 is essential for neutrophil transmigration across the infected urothelium and that neutrophils are important for clearance of bacterial infections in the urinary tract (32). The role of ATP in the host response has not previously been addressed in the urinary tract.…”

mentioning

confidence: 99%

Extracellular ATP and P2Y Receptor Activation Induce a Proinflammatory Host Response in the Human Urinary Tract

Säve

Persson

2010

Infect Immun

View full text Add to dashboard Cite

Extracellular ATP is released from a variety of cells not only as a consequence of cell injury or cell death but also via nonlytic mechanisms (25). ATP has attracted increasing attention as a danger signal released during the initial phase of infection and inflammation in order to trigger innate immunity (18). In a healthy bladder, release of ATP from uroepithelial cells by stretch and distension mediates the sensation of bladder fullness by activation of P2X 3 receptors on suburothelial sensory nerves (5). Pathophysiological conditions cause enhanced bladder release of ATP as shown in patients diagnosed with interstitial cystitis (29,30,31). Although several studies have shown that pathology often results in augmented ATP release from the urothelium, there have not been any studies of ATP release from urothelium infected with bacteria. Patients with bacteriuria have increased urinary levels of ATP (21), but it is not known whether the bacteria, host, or both produce ATP during infection. In their function as extracellular mediators, nucleotides activate P2 nucleotide receptors that include the ionotrophic P2X receptors (P2X 1 to P2X 7 ) and G-proteincoupled P2Y receptors (P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , and P2Y 11 to P2Y 14 ) (33). In the urinary tract, extracellular ATP may communicate through P2X and P2Y receptors with different cells, such as uroepithelial cells, inflammatory cells, nerves, and myofibroblasts (5). Evidence that P2 receptors, in particular P2Y receptors, may regulate host immunity and modulate phagocytosis, chemotaxis, and cytokine production is now accumulating (14, 16). The P2Y receptor subtypes P2Y 1 , P2Y 2 , and P2Y 4 are expressed throughout the cat bladder urothelium (7), but P2Y receptor expression has not been examined in the human urothelium.Innate immunity is the first line of defense in the urinary tract and triggered by uropathogenic bacteria through activation of Toll-like receptors (TLRs) located on the uroepithelial cell surface (32). Lipopolysaccharide (LPS) is an established ligand for Toll-like receptor 4 (TLR4), but associated coeffector proteins, such as CD14 and MD2, are needed for LPS-induced stimulation of TLR4 (4, 27). TLR4 and CD14 expression by the human urinary tract epithelium remains controversial (3,23,24), and in vitro studies show that the TLR4 receptor can be activated in a LPS-independent manner by P-fimbriated uropathogenic Escherichia coli (UPEC) (12). Once activated, the uroepithelial cells play a central role in the host proinflammatory response through production of chemotactic substances, such as interleukin 6 (IL-6) and IL-8. Several lines of evidence demonstrate that IL-8 is essential for neutrophil transmigration across the infected urothelium and that neutrophils are important for clearance of bacterial infections in the urinary tract (32).

show abstract

Uropathogenic Escherichia coli as a model of host–parasite interaction

Cited by 99 publications

References 62 publications

Biological Trojan Horse: Antigen 43 Provides Specific Bacterial Uptake and Survival in Human Neutrophils

Biological Trojan Horse: Antigen 43 Provides Specific Bacterial Uptake and Survival in Human Neutrophils

Innate Transcriptional Networks Activated in Bladder in Response to Uropathogenic Escherichia coli Drive Diverse Biological Pathways and Rapid Synthesis of IL-10 for Defense against Bacterial Urinary Tract Infection

Extracellular ATP and P2Y Receptor Activation Induce a Proinflammatory Host Response in the Human Urinary Tract

Contact Info

Product

Resources

About