title: The Effects of CFTR and Mucoid Phenotype on Susceptibility and Innate Immune Responses in a Mouse Model of Pneumococcal Lung Disease.
abstract: Recent studies have reported the isolation of highly mucoid serotype 3 Streptococcus pneumoniae (Sp) from the respiratory tracts of children with cystic fibrosis (CF). Whether these highly mucoid Sp contribute to, or are associated with, respiratory failure among patients with CF remains unknown. Other mucoid bacteria, predominately Pseudomonas aeruginosa, are associated with CF respiratory decline. We used a mouse model of CF to study pneumococcal pneumonia with highly mucoid serotype 3 and non-mucoid serotype 19A Sp isolates. We investigated susceptibility to infection, survival, and bacterial counts from bronchoaviolar lavage samples and lung homogenates, as well as associated inflammatory cytokines at the site of infection, and lung pathology. Congenic CFTR-/- mice and wild-type (WT)-mice were infected intranasally with CHB756, CHB1126, and WU2 (highly mucoid capsular serotype 3, intermediately mucoid serotype 3, and less mucoid serotype 3, respectively), or CHB1058 (non-mucoid serotype 19A). BAL, lung homogenates, and blood were collected from mice 5 days post-infection. Higher CFU recovery and shorter survival were observed following infection of CFTR-/- mice with CHB756 compared to infection with CHB1126, WU2, or CHB1058 (P≤0.001). Additionally, CFTR-/- mice infected with CHB756 and CHB1126 were more susceptible to infection than WT-mice (P≤0.05). Between CFTR-/- mice and WT-mice, no significant differences in TNF-α, CXCL1/KC concentrations, or lung histopathology were observed. Our results indicate that highly mucoid type 3 Sp causes more severe lung disease than non-mucoid Sp, and does so more readily in the lungs of CFTR-/- than WT-mice.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Evida A
authors.initials: EA
authors.lastname: Dennis
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Biological Sciences, Alabama State University, Montgomery, Alabama, United States of America.
authors.forename: Mamie T
authors.initials: MT
authors.lastname: Coats
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Griffin
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Joanetha Y
authors.initials: JY
authors.lastname: Hale
authors.affiliation: Department of Anatomic Pathology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Lea
authors.initials: L
authors.lastname: Novak
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: David E
authors.initials: DE
authors.lastname: Briles
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Crain
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000382:microbiology; D054360:Chemokine CXCL1 / Q000378:metabolism; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D018181:Mice, Inbred CFTR / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D009154:Mutation; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C505032:CFTR protein, human; D054360:Chemokine CXCL1; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator