title: Airway epithelial MyD88 restores control of Pseudomonas aeruginosa murine infection via an IL-1-dependent pathway.
abstract: The opportunistic human pathogen Pseudomonas aeruginosa causes rapidly progressive and tissue-destructive infections, such as hospital-acquired and ventilator-associated pneumonias. Innate immune responses are critical in controlling P. aeruginosa in the mammalian lung, as demonstrated by the increased susceptibility of MyD88(-/-) mice to this pathogen. Experiments conducted using bone marrow chimeric mice demonstrated that radio-resistant cells participated in initiating MyD88-dependent innate immune responses to P. aeruginosa. In this study we used a novel transgenic mouse model to demonstrate that MyD88 expression by epithelial cells is sufficient to generate a rapid and protective innate immune response following intranasal infection with P. aeruginosa. MyD88 functions as an adaptor for many TLRs. However, mice in which multiple TLR pathways (e.g., TLR2/TLR4/TLR5) are blocked are not as compromised in their response to P. aeruginosa as mice lacking MyD88. We demonstrate that IL-1R signaling is an essential element of MyD88-dependent epithelial cell responses to P. aeruginosa infection.
authors.affiliation: Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Lilia A
authors.initials: LA
authors.lastname: Mijares
authors.forename: Tamding
authors.initials: T
authors.lastname: Wangdi
authors.forename: Caroline
authors.initials: C
authors.lastname: Sokol
authors.forename: Robert
authors.initials: R
authors.lastname: Homer
authors.forename: Ruslan
authors.initials: R
authors.lastname: Medzhitov
authors.forename: Barbara I
authors.initials: BI
authors.lastname: Kazmierczak
mesh_terms: D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D007375:Interleukin-1 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D007375:Interleukin-1; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88