title: SPLUNC1/BPIFA1 contributes to pulmonary host defense against Klebsiella pneumoniae respiratory infection.
abstract: Epithelial host defense proteins comprise a critical component of the pulmonary innate immune response to infection. The short palate, lung, nasal epithelium clone (PLUNC) 1 (SPLUNC1) protein is a member of the bactericidal/permeability-increasing (BPI) fold-containing (BPIF) protein family, sharing structural similarities with BPI-like proteins. SPLUNC1 is a 25 kDa secretory protein that is expressed in nasal, oropharyngeal, and lung epithelia, and has been implicated in airway host defense against Pseudomonas aeruginosa and other organisms. SPLUNC1 is reported to have surfactant properties, which may contribute to anti-biofilm defenses. The objective of this study was to assess the importance of SPLUNC1 surfactant activity in airway epithelial secretions and to explore its biological relevance in the context of a bacterial infection model. Using cultured airway epithelia, we confirmed that SPLUNC1 is critically important for maintenance of low surface tension in airway fluids. Furthermore, we demonstrated that recombinant SPLUNC1 (rSPLUNC1) significantly inhibited Klebsiella pneumoniae biofilm formation on airway epithelia. We subsequently found that Splunc1(-/-) mice were significantly more susceptible to infection with K. pneumoniae, confirming the likely in vivo relevance of this anti-biofilm effect. Our data indicate that SPLUNC1 is a crucial component of mucosal innate immune defense against pulmonary infection by a relevant airway pathogen, and provide further support for the novel hypothesis that SPLUNC1 protein prevents bacterial biofilm formation through its ability to modulate surface tension of airway fluids.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Bartlett
authors.forename: Marissa E
authors.initials: ME
authors.lastname: Di
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bomberger
authors.forename: Yvonne R
authors.initials: YR
authors.lastname: Chan
authors.forename: Lokesh
authors.initials: L
authors.lastname: Gakhar
authors.forename: Rama K
authors.initials: RK
authors.lastname: Mallampalli
authors.forename: Paul B
authors.initials: PB
authors.lastname: McCray
authors.forename: Y Peter
authors.initials: YP
authors.lastname: Di
mesh_terms: D000818:Animals; D001483:Base Sequence; D018441:Biofilms / Q000254:growth & development; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007710:Klebsiella Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D007711:Klebsiella pneumoniae / Q000254:growth & development / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D013500:Surface Tension; D015854:Up-Regulation
chemical_list: C485599:BPIFA1 protein, human; C119074:Bpifa1 protein, mouse; D016207:Cytokines; D006023:Glycoproteins; D018836:Inflammation Mediators; D010750:Phosphoproteins