Different strains of Pseudomonas aeruginosa isolated  from
ocular infections or inflammation display distinct corneal pathologies  in
an animal model

Cole, Nerida; Willcox, Mark; Fleiszig, Suzanne M. J.; Stapleton, F.; Bao, B.; Tout, S.; Husband, A J

doi:10.1076/ceyr.17.7.730.5166

Cited by 37 publications

(60 citation statements)

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“…3,46,47 Histologic assessment at days 3 and 7 was not possible, as the corneas perforated on enucleation. In addition to the clinical signs observed in the WT animals, PA keratitis in the KO mice presented with a grossly edematous and ectatic central cornea with ensuing descemetocele (keratocele) formation at the end stage of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…In the absence of timely and appropriate treatments, the infected cornea undergoes progressive degradation leading to perforation and therefore permanent vision loss. [3][4][5] The host immune response to PA corneal infection, which is critical in determining the outcome of the disease, consists primarily of an influx of neutrophils from the tear film and the limbal vasculature into the cornea. Previous studies suggest that both tissue-destructive bacterial proteases and stromal-degrading enzymes liberated by activated neutrophils and other stimulated inflammatory cells (e.g., macrophages) account for the corneal perforation observed in patients with severe PA keratitis.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

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Cathelicidin-Deficient (Cnlp⁻^/⁻) Mice Show Increased Susceptibility toPseudomonas aeruginosaKeratitis

Li-min

Reins

Gallo

et al. 2007

Invest. Ophthalmol. Vis. Sci.

100

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Purpose-To examine the clinical progression and innate immune responses during Pseudomonas aeruginosa (PA) keratitis in cathelicidin-deficient (KO) mice. (ATCC 19660) keratitis was induced in KO mice and wild-type (WT) littermates generated on a 129/SVJ background. Clinical score and histopathology were used to monitor the progression of infection at postinfection (PI) days 1, 3, 7, 14, and 21. Mouse corneas were harvested for viable bacteria quantitation, and myeloperoxidase (MPO) assays were performed to determine the number of infiltrating neutrophils. ELISA was used to quantitate interleukin (IL)-1β, IL-6, macrophage inflammatory peptide (MIP)-2, keratinocyte-derived chemokine (KC), tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) levels in the corneas. Methods-PAResults-WT mice were resistant (cornea healed), whereas KO mice showed increased susceptibility (corneas failed to recover by 21 days or perforated) to PA infection. Clinical scores were significantly elevated in the infected corneas of KO mice versus WT mice at 7, 14, and 21 days PI. Absence of cathelicidin resulted in significantly delayed clearance of PA in the cornea and an increased number of infiltrating neutrophils at 1, 3, 7, and 14 days PI. KO mice also exhibited differential expression of protein levels for IL-1β, IL-6, MIP-2, KC, TNF-α, and VEGF up to day 21 PI compared with the WT mice.Conclusions-Cathelicidin-deficient mice showed considerable susceptibility to PA keratitis. The present study demonstrates direct in vivo evidence that endogenous expression of cathelicidin provides defense against corneal PA infection indicating its importance in host innate immunity at the ocular surface.The bacterium Pseudomonas aeruginosa (PA) is one of the leading virulent corneal pathogens associated with contact lens-related keratitis. 1,2 Although an opportunistic organism, PA is notorious for its resistance to antibiotics and is therefore considered a particularly dangerous and dreaded ocular pathogen. PA induced ulcerative keratitis is a rapidly developing and devastating corneal disease that typically presents with severe inflammation, neovascularization, and liquefactive necrosis of the cornea. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript suppurative stromal ulceration and mucopurulent exudate, the clinical picture of advanced PA keratitis may also reveal descemetocele (keratocele) formation resulting from corneal melting. In the absence of timely and appropriate treatments, the infected cornea undergoes progressive degradation leading to perforation and therefore permanent vision loss. [3][4][5] The host immune response to PA corneal infection, which is critical in determining the outcome of the disease, consists primarily of an influx of neutrophils from the tear film and the limbal vasculature into the cornea. Previous studies suggest that both tissue-destructive bacterial proteases and stromal-degrading enzymes liberated by activated neutrophils and other stimulated inflamma...

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Section: Discussionmentioning

confidence: 99%

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Cathelicidin-Deficient (Cnlp⁻^/⁻) Mice Show Increased Susceptibility toPseudomonas aeruginosaKeratitis

Li-min

Reins

Gallo

et al. 2007

Invest. Ophthalmol. Vis. Sci.

100

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“…Stock cultures of P. aeruginosa 6206 and 6294 stored in 30% glycerol at Ϫ70°C were inoculated into 10 ml of tryptone soy broth (Oxoid Ltd., Sydney, Australia). These strains of bacteria are well-characterized corneal iso-lates from cases of microbial keratitis (12) which lead to distinct corneal pathologies in a mouse model (7). Fleiszig et al (12) have demonstrated that strain 6206 is toxic to mammalian cells but that strain 6294 is an invasive strain and is engulfed by mammalian cells.…”

Section: Methodsmentioning

confidence: 99%

“…IL-10 gene knockout mice generated on a C57BL/6 background and C57BL/6 wild-type control mouse breeding stocks were obtained from Jackson Laboratories (Bar Harbor, Maine) and housed under specific-pathogen-free conditions at the Biological Resources Center, University of New South Wales, Sydney, Australia. Inbred 6-to 8-week-old mice were challenged with P. aeruginosa as previously described (7). The mice were examined for signs of systemic disease prior to the commencement of experiments, and only healthy mice were used for experiments.…”

Section: Methodsmentioning

confidence: 99%

ExperimentalPseudomonas aeruginosaKeratitis in Interleukin-10 Gene Knockout Mice

et al. 2003

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Pseudomonas aeruginosa keratitis is one of the most destructive diseases of the cornea. The host response to this infection is critical to the outcome. The cytokine interleukin-10 (IL-10) is thought to play an important role in modulating excessive inflammation and antimicrobial defenses. We have found that in IL-10 ؊/؊ mice there is a significant decrease in bacterial load in corneas at 7 days postchallenge with P. aeruginosa. This decrease was accompanied by a reduction in neutrophil numbers in the cornea and changes in cytokine levels compared to those of wild-type mice. A characteristic increase in neovascularization in the cornea was found in the IL-10 ؊/؊ mice. This increased angiogenesis correlated with an increased expression of KC, whereas the kinetics of macrophage inflammatory peptide 2 expression correlated with neutrophil numbers. This finding suggests that KC may play a role in corneal angiogenesis. The source of IL-10 in mouse corneas was identified as a subpopulation of infiltrating cells and keratocytes. This study demonstrates that IL-10 plays an important role in regulating the balance of inflammatory mediators during P. aeruginosa infection of the cornea.

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“…The cytotoxic strain 6206 of P. aeruginosa was used. Strain 6206 was isolated from a human corneal ulcer and classified as a cytotoxic strain on the basis of its interaction with corneal epithelial cells in vitro (8). Bacteria were grown in 10 ml of tryptone soy broth (Oxoid Ltd., Sydney, Australia) overnight at 37°C, harvested and washed three times in sterile phosphate-buffered saline (PBS), and resuspended in PBS prior to use.…”

Section: Methodsmentioning

confidence: 99%

Effector Mechanisms of Protection againstPseudomonas aeruginosaKeratitis in Immunized Rats

et al. 2001

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Pseudomonas aeruginosa is an opportunistic pathogen which causes sight-threatening corneal infections in humans. The purpose of this study was to evaluate various immunization routes that may provide protection against Pseudomonas keratitis and to define the molecular mechanisms involved in the protection. SpragueDawley rats (10 to 12 weeks old) were immunized using paraformaldehyde-killed P. aeruginosa (strain 6206) via oral, nasal, and intra-Peyer's patch (IPP) routes followed by an ocular topical booster dose. Scratched corneas were challenged with an infective dose of P. aeruginosa. Following clinical examination, eyes were enucleated for histology, polymorphonuclear leukocyte (PMN) quantitation, bacterial count, enzyme-linked immunosorbent assay, and RNase protection assay. PMN infiltration was higher early (4 h) during the infection in immunized rats than in nonimmunized rats. Later during the infection, the number of PMNs diminished in immunized rats while in nonimmunized animals the number of PMNs continued to increase. Bacteria were cleared much faster from immunized groups than from the nonimmunized group, and the nasally immunized group had the most efficacious response among the immunized groups. Nasal and IPP immunization groups had increased cytokine expression of interleukin-2 (IL-2) and IL-5 and differed from each other for IL-6. All three immunized groups had significantly reduced IL-1␤ levels when compared with the nonimmunized rats and a significantly altered profile for CINC-1 expression. This study has shown that the route of immunization modulates the inflammatory response to ocular P. aeruginosa infection, thus affecting the severity of keratitis and adverse pathology, with nasal immunization being the most effective.

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Different strains of Pseudomonas aeruginosa isolated from ocular infections or inflammation display distinct corneal pathologies in an animal model

Abstract: This study has identified that P. aeruginosa produces at least three different types of corneal pathology and that not all strains are able to infect mouse corneas.

Cited by 37 publications

References 0 publications

Cathelicidin-Deficient (Cnlp⁻^/⁻) Mice Show Increased Susceptibility toPseudomonas aeruginosaKeratitis

Cathelicidin-Deficient (Cnlp⁻^/⁻) Mice Show Increased Susceptibility toPseudomonas aeruginosaKeratitis

ExperimentalPseudomonas aeruginosaKeratitis in Interleukin-10 Gene Knockout Mice

Effector Mechanisms of Protection againstPseudomonas aeruginosaKeratitis in Immunized Rats

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Different strains of Pseudomonas aeruginosa isolated from ocular infections or inflammation display distinct corneal pathologies in an animal model

Abstract: This study has identified that P. aeruginosa produces at least three different types of corneal pathology and that not all strains are able to infect mouse corneas.

Cited by 37 publications

References 0 publications

Cathelicidin-Deficient (Cnlp−/−) Mice Show Increased Susceptibility toPseudomonas aeruginosaKeratitis

Cathelicidin-Deficient (Cnlp−/−) Mice Show Increased Susceptibility toPseudomonas aeruginosaKeratitis

ExperimentalPseudomonas aeruginosaKeratitis in Interleukin-10 Gene Knockout Mice

Effector Mechanisms of Protection againstPseudomonas aeruginosaKeratitis in Immunized Rats

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Product

Resources

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Cathelicidin-Deficient (Cnlp⁻^/⁻) Mice Show Increased Susceptibility toPseudomonas aeruginosaKeratitis

Cathelicidin-Deficient (Cnlp⁻^/⁻) Mice Show Increased Susceptibility toPseudomonas aeruginosaKeratitis