title: CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection.
abstract: 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.
authors.affiliation: Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA.
authors.forename: Tanweer
authors.initials: T
authors.lastname: Zaidi
authors.forename: Thomas
authors.initials: T
authors.lastname: Reidy
authors.forename: Samantha
authors.initials: S
authors.lastname: D'Ortona
authors.forename: Raina
authors.initials: R
authors.lastname: Fichorova
authors.forename: Gerald
authors.initials: G
authors.lastname: Pier
authors.forename: Mihaela
authors.initials: M
authors.lastname: Gadjeva
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015817:Eye Infections / Q000276:immunology* / Q000382:microbiology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; C045084:invariant chain