Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis.

Pseudomonas aeruginosa causes severe sight-threatening corneal infections, with the inflammatory response to the pathogen being the major factor resulting in damage to the cornea that leads to loss of visual acuity. We found that mice deficient for macrophage migration inhibitory factor (MIF), a key...

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Autores principales:	Mihaela Gadjeva, Jill Nagashima, Tanweer Zaidi, Robert A Mitchell, Gerald B Pier
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/89484f0a4a9b4865a2ec35887ca11d8a
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spelling	oai:doaj.org-article:89484f0a4a9b4865a2ec35887ca11d8a2021-11-25T05:48:12ZInhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis.1553-73661553-737410.1371/journal.ppat.1000826https://doaj.org/article/89484f0a4a9b4865a2ec35887ca11d8a2010-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20361053/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Pseudomonas aeruginosa causes severe sight-threatening corneal infections, with the inflammatory response to the pathogen being the major factor resulting in damage to the cornea that leads to loss of visual acuity. We found that mice deficient for macrophage migration inhibitory factor (MIF), a key regulator of inflammation, had significantly reduced consequences from acute P. aeruginosa keratitis. This improvement in the outcome was manifested as improved bacterial clearance, decreased neutrophil infiltration, and decreased inflammatory responses when P. aeruginosa-infected MIF knock out (KO) mice were compared to infected wild-type mice. Recombinant MIF applied to infected corneas restored the susceptibility of MIF deficient mice to P. aeruginosa-induced disease, demonstrating that MIF is necessary and sufficient to cause significant pathology at this immune privileged site. A MIF inhibitor administered during P. aeruginosa-induced infection ameliorated the disease-associated pathology. MIF regulated epithelial cell responses to infection by enhancing synthesis of proinflammatory mediators in response to P. aeruginosa infection and by promoting bacterial invasion of corneal epithelial cells, a correlate of virulence in the keratitis model. Our results uncover a host factor that elevates inflammation and propagates bacterial cellular invasion, and further suggest that inhibition of MIF during infection may have a beneficial therapeutic effect.Mihaela GadjevaJill NagashimaTanweer ZaidiRobert A MitchellGerald B PierPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 3, p e1000826 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Mihaela Gadjeva Jill Nagashima Tanweer Zaidi Robert A Mitchell Gerald B Pier Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis.
description	Pseudomonas aeruginosa causes severe sight-threatening corneal infections, with the inflammatory response to the pathogen being the major factor resulting in damage to the cornea that leads to loss of visual acuity. We found that mice deficient for macrophage migration inhibitory factor (MIF), a key regulator of inflammation, had significantly reduced consequences from acute P. aeruginosa keratitis. This improvement in the outcome was manifested as improved bacterial clearance, decreased neutrophil infiltration, and decreased inflammatory responses when P. aeruginosa-infected MIF knock out (KO) mice were compared to infected wild-type mice. Recombinant MIF applied to infected corneas restored the susceptibility of MIF deficient mice to P. aeruginosa-induced disease, demonstrating that MIF is necessary and sufficient to cause significant pathology at this immune privileged site. A MIF inhibitor administered during P. aeruginosa-induced infection ameliorated the disease-associated pathology. MIF regulated epithelial cell responses to infection by enhancing synthesis of proinflammatory mediators in response to P. aeruginosa infection and by promoting bacterial invasion of corneal epithelial cells, a correlate of virulence in the keratitis model. Our results uncover a host factor that elevates inflammation and propagates bacterial cellular invasion, and further suggest that inhibition of MIF during infection may have a beneficial therapeutic effect.
format	article
author	Mihaela Gadjeva Jill Nagashima Tanweer Zaidi Robert A Mitchell Gerald B Pier
author_facet	Mihaela Gadjeva Jill Nagashima Tanweer Zaidi Robert A Mitchell Gerald B Pier
author_sort	Mihaela Gadjeva
title	Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis.
title_short	Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis.
title_full	Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis.
title_fullStr	Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis.
title_full_unstemmed	Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis.
title_sort	inhibition of macrophage migration inhibitory factor ameliorates ocular pseudomonas aeruginosa-induced keratitis.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/89484f0a4a9b4865a2ec35887ca11d8a
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Inhibition of macrophage migration inhibitory factor ameliorates ocular Pseudomonas aeruginosa-induced keratitis.

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