IL-24 Promotes Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas

Ross, Bing X; Gao, Nan; Cui, Xinhan; Standiford, Theodore J.; Xu, Jianjiang; Yu, Fei

doi:10.4049/jimmunol.1602087

Cited by 25 publications

(12 citation statements)

References 58 publications

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“…Using antibody neutralization, we showed that downregulating TSLP-TSLPR signaling significantly augmented corneal opacification, clinical scores, bacterial burden, PMN infiltration, and the expression of IL-1β at 3 dpi. The bacterial plate counts for the controls of P. aeruginosa toxic strain at 3 dpi are within the ranges reported in the literature 31 , 32 as well as our previous studies, 18 , 26 even though the number of bacteria used to inoculate the mouse corneas were 100-fold less than that used by others. 21 , 31 The differences in the detected bacterial burden between the control and TSLPR-neutralized corneas at 3 dpi (∼10 fold with P = 0.0198) is comparable to our previous study of the corneas treated with recombinant IL-24.…”

Section: Discussionsupporting

confidence: 87%

“…At 3 dpi, heavy opacity covered the entire cornea with corneal ulceration, melting ring, and neovascularization (reddish color), pathologies usually seen in the control corneas at day 5. 18 , 26 The clinical scores revealed significantly higher disease severity in the TSLPR neutralizing antibody-treated group than that observed in the IgG injected control group (6.2 vs. 11.6 at 3 dpi; Fig. 4 A).…”

Section: Resultsmentioning

confidence: 87%

“…21 , 31 The differences in the detected bacterial burden between the control and TSLPR-neutralized corneas at 3 dpi (∼10 fold with P = 0.0198) is comparable to our previous study of the corneas treated with recombinant IL-24. 26 Together, these parameters—opacification shown in micrograph, clinical scoring, bacterial plate counting, MPO measurement, and proinflammatory cytokine detection—revealed a significant increase in the severity of keratitis in B6 mice. In the literature, TSLP has been shown to enhance neutrophil killing of methicillin-resistant Staphylococcus aureus without affecting TH2 responses during an in vivo skin infection.…”

Section: Discussionmentioning

confidence: 92%

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TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

Cui

Gao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeWe sought to determine the role of epithelium-produced thymic stromal lymphopoietin (TSLP) and its underlying mechanisms in corneal innate immune defense against Pseudomonas (P.) aeruginosa keratitis.MethodsThe expression of TSLP and TSLPR in cultured human corneal epithelial cells (HCECs) and mouse corneas was determined by PCR, Western, and/or ELISA. Cellular localization of TSLP receptor (TSLPR) was determined by whole mount confocal microscopy. TSLP-TSLPR signaling was downregulated by neutralizing antibodies and/or small interfering (si)RNA; their effects on the severity of P. aeruginosa–keratitis and cytokine expression were assessed using clinical scoring, bacterial counting, PMN infiltration, and real-time PCR. The role of dendritic cells (DCs) in corneal innate immunity was determined by local DC depletion using CD11c-DTR mice.ResultsP. aeruginosa–infection induced the expression of TSLP and TSLPR in both cultured primary HCECs and in C57BL/6 mouse corneas. While TSLP was mostly expressed by epithelial cells, CD11c-positive cells were positive for TSLPR. Targeting TSLP or TSLPR with neutralizing antibodies or TSLPR with siRNA resulted in more severe keratitis, attributable to an increase in bacterial burden and PMN infiltration. TSLPR neutralization significantly suppressed infection-induced TSLP and interleukin (IL)-17C expression and augmented the expression of IL-23 and IL-17A. Local depletion of DCs markedly increased the severity of keratitis and exhibited no effects on TSLP and IL-23 expression while suppressing IL-17A and C expression in P. aeruginosa–infected corneas.ConclusionsThe epithelium-expressed TSLP plays a protective role in P. aeruginosa keratitis through targeting of DCs and in an IL-23/IL-17 signaling pathway-related manner.

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Section: Discussionsupporting

confidence: 87%

Section: Resultsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 92%

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TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

Cui

Gao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Many organisms, including P. aeruginosa , are able to undergo mutation to acquire resistance to antimicrobial peptides, which would enhance their ability to persistently infect epithelial surfaces. An important site of P. aeruginosa infection is the eye, where these organisms are an important cause of keratitis [34, 35]. A major therapeutic strategy against these biofilm infections is the development of optimized antimicrobial peptides delivered topically [36].…”

Section: P Aeruginosa Resistance To Antimicrobial Peptidesmentioning

confidence: 99%

Pseudomonas aeruginosa and Klebsiella pneumoniae Adaptation to Innate Immune Clearance Mechanisms in the Lung

Riquelme¹,

Ahn²,

Prince³

2018

J Innate Immun

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Many different species of gram-negative bacteria are associated with infection in the lung, causing exacerbations of chronic obstructive pulmonary disease, cystic fibrosis (CF), and ventilator-associated pneumonias. These airway pathogens must adapt to common host clearance mechanisms that include killing by antimicrobial peptides, antibiotics, oxidative stress, and phagocytosis by leukocytes. Bacterial adaptation to the host is often evident phenotypically, with increased extracellular polysaccharide production characteristic of some biofilm-associated organisms. Given the relatively limited repertoire of bacterial strategies to elude airway defenses, it seems likely that organisms sharing the same ecological niche might also share common strategies to persistently infect the lung. In this review, we will highlight some of the major factors responsible for the adaptation of Pseudomonas aeruginosa to the lung, addressing how growth in biofilms enables persistent infection, relevant to, but not limited to, the pathogenesis of infection in CF. In contrast, we will discuss how carbapenem-resistant Klebsiella pneumoniae evade immune clearance, an organism often associated with ventilator-associated pneumonia and health-care-acquired pneumonias, but not a typical pathogen in CF.

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“…Unlike IL-20, IL-24 may suppress mucosal inflammation by inducing suppressor of cytokine signaling (SOCS) 3 expression in HT-29 colonic epithelial cells and membrane-bound mucin (MUC)-1, −3, and −4 in human colonic subepithelial myofibroblasts obtained from patients with IBD [44]. IL-24 also exacerbates Pseudomonas aeruginosa infection in mouse corneas by promoting SOCS3 expression, which leads to the suppression of anti-bacterial molecules expression, including S100A8/A9 and IL-1β [48]. …”

Section: Immunobiology Of the Il-20r Cytokinesmentioning

confidence: 99%

IL-20 receptor cytokines in autoimmune diseases

Chen

Caspi

Chong

2018

Journal of Leukocyte Biology

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IL-19, IL-20, and IL-24 are the members of IL-10 family. They are also known as IL-20 receptor (IL-20R) cytokines as they all signal through the IL-20RA/IL-20RB receptor complex; IL-20 and IL-24 (but not IL-19) also signal through the IL-20RB/IL22RA1 receptor complex. Despite their protein structure homology and shared use of receptor complexes, they display distinct biological functions in immune regulation, tissue homeostasis, host defense, and oncogenesis. IL-20R cytokines can be expressed by both immune cells and epithelial cells, and are important for their interaction. In general, these cytokines are considered to be associated with pathogenesis of chronic inflammation and autoimmune diseases, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. However, a number of studies also highlighted their suppressive functions in regulating both innate and adaptive T cell responses and other immune cells, suggesting that the role of IL-20R cytokines in autoimmunity may be complex. In this review, we will discuss the immunobiological functions of IL-20R cytokines and how they are involved in regulating autoimmune diseases.

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IL-24 Promotes Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas

Cited by 25 publications

References 58 publications

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

<b><i>Pseudomonas aeruginosa</i></b> and <b><i>Klebsiella</i></b> <b><i>pneumoniae</i></b> Adaptation to Innate Immune Clearance Mechanisms in the Lung

IL-20 receptor cytokines in autoimmune diseases

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