Development of experimental model of chronic pyelonephritis with Escherichia coli O75:K5:H-bearing Dr fimbriae: mutation in the dra region prevented tubulointerstitial nephritis.

Goluszko, Pawel; Moseley, Steve L.; Truong, Luan D.; Kaul, Anil; Williford, John R; Selvarangan, Rangaraj; Nowicki, Stella; Nowicki, B.

doi:10.1172/jci119329

Cited by 114 publications

(143 citation statements)

References 40 publications

(31 reference statements)

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“…Our group and other researchers have demonstrated that NO is produced by a variety of uterine cell types, including endometrial epithelium, metrial glands, decidua, myometrial cells, NK cells, and macrophages (6,7,28,38,40). Previous work has also implicated NO as a modulator of uterine infection, including the finding that NO inhibition increased the lethality of experimental intrauterine infection in pregnant rats and that intrauterine infection results in a localized increase in NO synthesis (9,30). These data, together with the observation that the uterine endometrium expresses both NOS II and NOS III (38), suggested that endogenous NO may be involved in the uterine defense against bacterial infection.…”

Section: Discussionmentioning

confidence: 73%

“…To assess the effects of NO on bacterial invasion and internalization in Ishikawa cells, we used a Dr ϩ fimbriated clinical isolate of E. coli (strain IH11128 [O75:K5:H Ϫ ])or its Dr Ϫ mutant E. coli Dr 14 (9). In addition, we used a recombinant strain, BN406 (the laboratory E. coli K-12 strain carrying plasmid pBJN406), encoding the production of Dr fimbriae, and the recombinant E. coli K-12 strain BN17, containing a transposon insertion mutation in the draE gene (Dr Ϫ phenotype) (9,10,31). Because the cellular receptor of Dr ϩ fimbriated E. coli, DAF, was shown to be expressed in epithelial cells, we initially confirmed the expression of DAF in Ishikawa cells.…”

Section: Methodsmentioning

confidence: 99%

“…Then, bacterial suspensions in 500 l of PBS, prepared as described previously (9,10) for the adherence assay, were added to monolayers of Ishikawa cells. The plates were then incubated at 37°C in a CO 2 incubator.…”

Section: Methodsmentioning

confidence: 99%

“…About 25 l of the lysate was plated on Luria agar plates and incubated overnight at 37°C under 5% CO 2 . The following day, the colonies were counted, and the results are expressed as bacterial CFU per well (9,10).…”

Section: Methodsmentioning

confidence: 99%

“…The data on bacterial internalization in Ishikawa cells were analyzed using analysis of variance followed by the Bonferroni test. The Mann-Whitney U test was used when the data were nonparametrically distributed (9,33). One-way analysis of variance or Student's t test was used to evaluate differences in the intensities of bands from various treatments.…”

Section: Methodsmentioning

confidence: 99%

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Epithelial Invasion by Escherichia coli Bearing Dr Fimbriae Is Controlled by Nitric Oxide-Regulated Expression of CD55

Li¹,

Nowicki

Urvil³

et al. 2004

Infect Immun

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We previously reported that inhibition of nitric oxide (NO) increases the rate of bacteremia and maternal mortality in pregnant rats with uterine infection by Escherichia coli expressing the Dr fimbria (Dr ؉ ). Epithelial binding and invasion by Dr ؉ E. coli has also been shown to be dependent upon the expression level of the cellular receptor decay-accelerating factor (DAF; CD55). Here, we hypothesize that NO-related severity of infection could be mediated by changes in DAF expression and in the rate of epithelial invasion. The cellular basis of NO effects on epithelial invasion with Dr ؉ E. coli was studied using Ishikawa endometrial carcinoma cells as an in vitro model of the human endometrial epithelium. Initially, we show that Ishikawa cells produce NO and express both NO synthase enzymes, NOS II and NOS III, and DAF protein. We next tested the abilities of both Dr ؉ E. coli and a Dr ؊ E. coli mutant to invade Ishikawa cells, and invasion was seen only with Dr ؉ E. coli. Invasion by Dr ؉ E. coli was decreased by elevated NO production and increased by NO inhibition. Elevated NO production significantly decreased DAF protein and mRNA expression in Ishikawa cells in a time-and dose-dependent manner. Here, we propose that in vitro invasion of an epithelial cell line is directly related to NO-regulated expression of DAF. The significance of NO-regulated receptor-ligand invasion is that it may represent a novel unrecognized phenomenon of epithelial defense against infection.Although urogenital microbial infection in pregnancy is an important cause of maternal and neonatal morbidity and mortality, the mechanisms of defense against gestational intrauterine infection are poorly understood (8,14,23). Evidence obtained in studies of both humans and rats suggests that the bacteriostatic actions of nitric oxide (NO) are an important component of defense against urogenital infection (16,30,33). Nitric oxide is synthesized in situ from an L-arginine substrate by one or more of three NO synthase isoforms (NOS I, NOS II, and NOS III), each of which has been identified in the mouse, rat, and human (1,27,40,41).Several lines of evidence have demonstrated the involvement of intracellular NO in the host defense mechanisms against bacterial infections (5, 27). Recently, NO production and three NOS isoforms were reported to be present in rat uterine tissues, and elevated NOS II expression was demonstrated to contribute to the increased NO production in the rat uterus and consequent uterine quiescence during gestation (3, 4, 40). However, the role of the NO system in uterine defense mechanisms is not well understood.Three separate lines of evidence from our laboratories have suggested that increased NO production by the urogenital tract in pregnancy protects against Escherichia coli infection. First, inhibition of NO synthesis in pregnant rats with an intrauterine infection increases maternal death (30). Second, the sensitivity of the female rat or mouse urinary tract to E. coli infection was increased with inhibition of NO (30,3...

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Section: Discussionmentioning

confidence: 73%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Epithelial Invasion by Escherichia coli Bearing Dr Fimbriae Is Controlled by Nitric Oxide-Regulated Expression of CD55

Li¹,

Nowicki

Urvil³

et al. 2004

Infect Immun

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DAF as a Therapeutic Target for Steroid Hormones: Implications for Host–Pathogen Interactions

Nowicki

2012

Complement Therapeutics

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In this chapter, we present a concise historic prospective and a summary of accumulated knowledge on steroid hormones, DAF expression, and therapeutic implication of steroid hormone treatment on multiple pathologies, including infection and the host-pathogen interactions. DAF/CD55 plays multiple physiologic functions including tissue protection from the cytotoxic complement injury, an anti-inflammatory function due to its anti-adherence properties which enhance transmigration of monocytes and macrophages and reduce tissue injury. DAF physiologic functions are essential in many organ systems including pregnancy for protection of the semiallogeneic fetus or for preventing uncontrolled infiltration by white cells in their pro- and/or anti-inflammatory functions. DAF expression appears to have multiple regulatory tissue-specific and/or menstrual cycle-specific mechanisms, which involve complex signaling mechanisms. Regulation of DAF expression may involve a direct or an indirect effect of at least the estrogen, progesterone, and corticosteroid regulatory pathways. DAF is exploited in multiple pathologic conditions by pathogens and viruses in chronic tissue infection processes. The binding of Escherichia coli bearing Dr adhesins to the DAF/CD55 receptor is DAF density dependent and triggers internalization of E. coli via an endocytic pathway involving CD55, lipid rafts, and microtubules. Dr+ E. coli or Dr antigen may persist in vivo in the interstitium for several months. Further understanding of such processes should be instrumental in designing therapeutic strategies for multiple conditions involving DAF's protective or pathologic functions and tailoring host expression of DAF.

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Urinary Tract Infections

2013

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Development of experimental model of chronic pyelonephritis with Escherichia coli O75:K5:H-bearing Dr fimbriae: mutation in the dra region prevented tubulointerstitial nephritis.

Cited by 114 publications

References 40 publications

Epithelial Invasion by Escherichia coli Bearing Dr Fimbriae Is Controlled by Nitric Oxide-Regulated Expression of CD55

Epithelial Invasion by Escherichia coli Bearing Dr Fimbriae Is Controlled by Nitric Oxide-Regulated Expression of CD55

DAF as a Therapeutic Target for Steroid Hormones: Implications for Host–Pathogen Interactions

Urinary Tract Infections

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