Interleukin-6 response of epithelial cell lines to bacterial stimulation in vitro

Hedges, Spencer R.; Svensson, Majlis; Svanborg, Catharina

doi:10.1128/iai.60.4.1295-1301.1992

Cited by 216 publications

(86 citation statements)

References 24 publications

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“…The fimbriae stimulate mucosal inflammation and the production of inflammatory mediators by epithelial cells. Although fimbriae themselves can trigger cell activation (Hedges et al, 1992;Svensson et al, 1994;Hedlund et al, 1996), they also dock the bacteria to sites at which receptors are expressed and may influence the host response by presenting other bacterial components, such as LPS, to these receptors. This study demonstrated that type 1 fimbriae deliver LPS to CD14-negative host cells and that the responses are partly TLR4 dependent.…”

Section: Discussionmentioning

confidence: 99%

Type 1 fimbriae deliver an LPS‐ and TLR4‐dependent activation signal to CD14‐negative cells

Hedlund¹,

Frendéus

Wachtler

et al. 2001

Molecular Microbiology

118

108

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SummaryFimbriae target bacteria to different mucosal surfaces and enhance the inflammatory response at these sites. Inflammation may be triggered by the fimbriae themselves or by fimbriae-dependent delivery of other host activating molecules such as lipopolysaccharide (LPS). Although LPS activates systemic inflammation through the CD14 and Toll-like receptor 4 (TLR4) pathways, mechanisms of epithelial cell activation by LPS are not well understood. These cells lack CD14 receptors and are unresponsive to pure LPS, but fimbriated Escherichia coli overcome this refractoriness and trigger epithelial cytokine responses. We now show that type 1 fimbriae can present an LPS-and TLR4-dependent signal to the CD14-negative epithelial cells. Human uroepithelial cells were shown to express TLR4, and type 1 fimbriated E. coli strains triggered an LPS-dependent response in those cells. A similar LPS-and fimbriaedependent response was observed in the urinary tract of TLR4-proficient mice, but not in TLR4-defective mice. The moderate inflammatory response in the TLR4-defective mice was fimbriae dependent but LPS independent. The results demonstrate that type 1 fimbriae present LPS to CD14-negative cells and that the TLR4 genotype determines this response despite the absence of CD14 on the target cells. The results illustrate how the host`sees' LPS and other microbial products not as purified molecules but as complexes, and that fimbriae determine the molecular context in which LPS is presented to host cells.

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Section: Discussionmentioning

confidence: 99%

Type 1 fimbriae deliver an LPS‐ and TLR4‐dependent activation signal to CD14‐negative cells

Hedlund¹,

Frendéus

Wachtler

et al. 2001

Molecular Microbiology

118

108

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“…A number of intriguing hypotheses involving the role of P fimbriae in UTI have been suggested. Svanborg and colleagues (Hedges ef a/., 1991;1992;Under ef a/., 1988;1990) propose that induction of inflammation including recruitment of potymorphonuclear leucocytes and triggering of secretion of interleukin-6 is caused by the delivery of lipopolysaccharide (LPS) by bacteria adhering by P To our knowledge, true isogenic mutants of pap have not previously been constructed in virulent clinical isolates of E. coii. However, the contribution to virulence of P fimbriae has been tested using various mutants and transformants.…”

Section: Discussionmentioning

confidence: 99%

Isogenic P‐fimbrial deletion mutants of pyelonephritogenic Escherichia coli: the role of α Gal(1–4)β Gal binding in virulence of a wild‐type strain

Mobley

Jarvis

Elwood

et al. 1993

Molecular Microbiology

171

148

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Escherichia coli strains causing acute pyelonephritis often express multiple fimbrial types and haemolysin, which may contribute to their ability to adhere to, and interact with, kidney epithelial cells. Strain CFT073, a pap+, sfa+, pil+, hly+ pyelonephritis strain, previously established as virulent in the CBA mouse model of ascending urinary tract infection and cytotoxic for cultured human renal epithelial cells, was selected for construction of isogenic strains. From a gene bank of this strain, two distinct copies of the pap operon were isolated. The two P-fimbrial determinants were subcloned into pCVD442, a positive selection suicide vector containing the sacB gene of Bacillus subtilis. Deletion mutations were introduced into each of the two constructs, within papEFG of one operon and papDEFG of the other. Suicide vectors carrying pap deletions were mobilized from E. coli SM10 lambda pir into CFT073 (NalR) and cointegrates were passaged on non-selective medium. The first pap mutation was identified by screening a Southern blot of DNA from sucrose-resistant colonies using a papEFG probe. This mutant retained the MRHA+ phenotype since a second functional copy of pap was still present. A double pap-deletion mutant, UPEC76, confirmed by Southern blotting, was unable to agglutinate human type O erythrocytes or alpha Gal(1-4)beta Gal-coated latex beads. CBA mice (N = 100) were challenged transurethrally with 10(5), 10(6), 10(7), or 10(9) cfu of strains CFT073 or UPEC76. After one week, quantitative cultures of urine, bladder, and kidney were done and histologic changes were examined. No substantive differences in organism concentration or histological findings between parent and mutant were detected in urine, bladder, or kidney at any challenge concentration. We conclude that adherence by P fimbriae of uropathogenic E. coli strain CFT073 plays only a subtle role in the development of acute pyelonephritis in the CBA mouse model.

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“…Many cell types produce this potent protein [41][42][43][44][45][46], and elevated levels of IL-6 are found in several different conditions [47][48][49][50][51][52][53]. Bacterial products [54,55] and various viruses [56,57] stimulate IL-6 production. High levels could be due to differences in responses to various stimuli, genetic polymorphisms, or a deficient interplay in the cytokine network, for instance with reduced production of IL-10 [58,59].…”

Section: Factors That Increases Il-6 Levelsmentioning

confidence: 99%

Sudden infant death syndrome, infection and inflammatory responses

VEGE

2004

FEMS Immunology and Medical Microbiology

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Sudden infant death syndrome (SIDS) is sudden unexpected death in infancy for which there is no explanation after review of the history, a death scene investigation and a thorough autopsy. The use of common diagnostic criteria is a prerequisite for discussing the importance of infection, inflammatory responses and trigger mechanism in SIDS. Several observations of immune stimulation in the periphery and of interleukin-6 elevation in the cerebrospinal fluid of SIDS victims explain how infections can play a role in precipitating these deaths. Finally, these findings and important risk factors for SIDS are integrated in the concept of a vicious circle for understanding the death mechanism. The vicious circle is a concept to elucidate the interactions between unfavourable factors, including deficient auto-resuscitation, and how this could result in death.

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Interleukin-6 response of epithelial cell lines to bacterial stimulation in vitro

Cited by 216 publications

References 24 publications

Type 1 fimbriae deliver an LPS‐ and TLR4‐dependent activation signal to CD14‐negative cells

Type 1 fimbriae deliver an LPS‐ and TLR4‐dependent activation signal to CD14‐negative cells

Isogenic P‐fimbrial deletion mutants of pyelonephritogenic Escherichia coli: the role of α Gal(1–4)β Gal binding in virulence of a wild‐type strain

Sudden infant death syndrome, infection and inflammatory responses

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