Neutrophil-Mediated Phagocytic Host Defense Defect in Myeloid Cftr-Inactivated Mice

• DOI: 10.1371/journal.pone.0106813
• Publication Date: 2014-09-03T18:14:25Z
• Authors: Hang Pong Ng; Yun Zhou; Kejing Song; Craig A. Hodges; Mitchell L. Drumm; Guoshun Wang
• Keywords: Mice, Knockout; 0301 basic medicine; Neutrophils; Science; Q; R; Cystic Fibrosis Transmembrane Conductance Regulator; Hypochlorous Acid; 3. Good health; Mice; 03 medical and health sciences; Phagocytosis; Phagosomes; Pseudomonas aeruginosa; Pneumonia, Bacterial; Medicine; Animals; Humans; Pseudomonas Infections; Research Article

Cystic fibrosis (CF) is a common and deadly inherited disease, caused by mutations in the CFTR gene that encodes cAMP-activated chloride channel. One outstanding manifestation of disease persistent bacterial infection inflammation lung, which claims over 90% CF mortality. It has been debated whether neutrophil-mediated phagocytic innate immunity any intrinsic defect contributes to host lung defense failure. Here we compared phagosomal targeting, hypochlorous acid (HOCl) production, microbial killing neutrophils from myeloid Cftr-inactivated (Myeloid-Cftr-/-) mice non-inactivated control (Cftrfl10) mice. We found mutant lacked Exon-10 failed target neutrophil phagosomes. This dysfunction resulted impaired intraphagosomal HOCl production killing. In vivo with lethal dose Pseudomonas aeruginosa significantly higher mortality than controls. The myeloid-Cftr-/- lungs were deficient clearance, had sustained neutrophilic stalled transition early late immunity. These manifestations recapitulated symptoms human lungs. data altogether suggest expression critical normal defense. compromises immunity, may predispose infection.