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CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection

Eye trauma and contact lens wear are the main factors that predispose to the development of infectious keratitis. The existing therapies fail to control the inflammation-driven tissue damage that occurs during Pseudomonas aeruginosa infection. Antibiotic treatment reduces bacterial burdens, but bett...

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Autores principales: Zaidi, Tanweer, Reidy, Thomas, D'Ortona, Samantha, Fichorova, Raina, Pier, Gerald, Gadjeva, Mihaela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216545/
https://www.ncbi.nlm.nih.gov/pubmed/22355577
http://dx.doi.org/10.1038/srep00058
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author Zaidi, Tanweer
Reidy, Thomas
D'Ortona, Samantha
Fichorova, Raina
Pier, Gerald
Gadjeva, Mihaela
author_facet Zaidi, Tanweer
Reidy, Thomas
D'Ortona, Samantha
Fichorova, Raina
Pier, Gerald
Gadjeva, Mihaela
author_sort Zaidi, Tanweer
collection PubMed
description Eye trauma and contact lens wear are the main factors that predispose to the development of infectious keratitis. The existing therapies fail to control the inflammation-driven tissue damage that occurs during Pseudomonas aeruginosa infection. Antibiotic treatment reduces bacterial burdens, but better interventions are needed to alleviate tissue damage resulting from local inflammation. We have previously documented that inhibition of macrophage migration inhibitory factor (MIF) reduces the bacterial levels and the inflammatory damage during keratitis. Here, we report that mice deficient for CD74, the putative MIF receptor, developed milder Pseudomonas aeruginosa-induced disease, characterized by decreased proinflammatory mediators and reduced bacterial presence in the cornea. However, topical inhibition of MIF using antibodies applied to the cornea further promoted recovery from disease, suggesting that in addition to MIF-dependent signaling events, MIF-triggered CD74-independent signaling pathways regulate sensitization to P. aeruginosa-induced infection.
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spelling pubmed-32165452011-12-22 CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection Zaidi, Tanweer Reidy, Thomas D'Ortona, Samantha Fichorova, Raina Pier, Gerald Gadjeva, Mihaela Sci Rep Article Eye trauma and contact lens wear are the main factors that predispose to the development of infectious keratitis. The existing therapies fail to control the inflammation-driven tissue damage that occurs during Pseudomonas aeruginosa infection. Antibiotic treatment reduces bacterial burdens, but better interventions are needed to alleviate tissue damage resulting from local inflammation. We have previously documented that inhibition of macrophage migration inhibitory factor (MIF) reduces the bacterial levels and the inflammatory damage during keratitis. Here, we report that mice deficient for CD74, the putative MIF receptor, developed milder Pseudomonas aeruginosa-induced disease, characterized by decreased proinflammatory mediators and reduced bacterial presence in the cornea. However, topical inhibition of MIF using antibodies applied to the cornea further promoted recovery from disease, suggesting that in addition to MIF-dependent signaling events, MIF-triggered CD74-independent signaling pathways regulate sensitization to P. aeruginosa-induced infection. Nature Publishing Group 2011-08-08 /pmc/articles/PMC3216545/ /pubmed/22355577 http://dx.doi.org/10.1038/srep00058 Text en Copyright © 2011, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Zaidi, Tanweer
Reidy, Thomas
D'Ortona, Samantha
Fichorova, Raina
Pier, Gerald
Gadjeva, Mihaela
CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection
title CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection
title_full CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection
title_fullStr CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection
title_full_unstemmed CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection
title_short CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection
title_sort cd74 deficiency ameliorates pseudomonas aeruginosa-induced ocular infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216545/
https://www.ncbi.nlm.nih.gov/pubmed/22355577
http://dx.doi.org/10.1038/srep00058
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