SPLUNC1/BPIFA1 Contributes to Pulmonary Host Defense against Klebsiella pneumoniae Respiratory Infection

• DOI: 10.1016/j.ajpath.2013.01.050
• Publication Date: 2013-03-15T17:14:00Z
• Authors: Yang Liu; Jennifer A. Bartlett; Marissa E. Di; Jennifer M. Bombe...; Yvonne R. Chan; Lokesh Gakhar; Rama K. Mallampalli; Paul B. McCray; Y. Peter Di
• Keywords: 0303 health sciences; Base Sequence; Molecular Sequence Data; Epithelial Cells; Phosphoproteins; Pathology and Forensic Medicine; Klebsiella Infections; Up-Regulation; 3. Good health; Klebsiella pneumoniae; Mice; 03 medical and health sciences; Biofilms; Host-Pathogen Interactions; Animals; Cytokines; Humans; Surface Tension; Disease Susceptibility; Inflammation Mediators; Lung; Respiratory Tract Infections; Glycoproteins

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 member bactericidal/permeability-increasing (BPI) fold-containing (BPIF) family, sharing structural similarities with BPI-like proteins. SPLUNC1 25 kDa secretory that expressed in nasal, oropharyngeal, and lung epithelia, has been implicated airway against Pseudomonas aeruginosa other organisms. reported have surfactant properties, which may contribute anti-biofilm defenses. objective this study was assess importance activity epithelial secretions explore its biological relevance context bacterial infection model. Using cultured we confirmed critically important for maintenance low surface tension fluids. Furthermore, demonstrated recombinant (rSPLUNC1) significantly inhibited Klebsiella pneumoniae biofilm formation on epithelia. We subsequently found Splunc1(-/-) mice were more susceptible K. pneumoniae, confirming likely vivo effect. Our data indicate crucial mucosal by relevant pathogen, provide further support novel hypothesis prevents through ability modulate