Morphine Disrupts Interleukin-23 (IL-23)/IL-17-Mediated Pulmonary Mucosal Host Defense against Streptococcus pneumoniae Infection

• DOI: 10.1128/iai.00914-09
• Publication Date: 2009-12-08T05:23:37Z
• Authors: Jing Ma; Jinghua Wang; Jing Wan; Richard Charboneau; Yaping Chang; Roderick A. Barke; Sabita Roy
• Keywords: Narcotics; 0303 health sciences; Morphine; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; Interleukin-17; Enzyme-Linked Immunosorbent Assay; Dendritic Cells; Respiratory Mucosa; Interleukin-23; Immunity, Innate; Pneumococcal Infections; 3. Good health; Mice; 03 medical and health sciences; Streptococcus pneumoniae; Macrophages, Alveolar; Animals; RNA, Messenger; Bronchoalveolar Lavage Fluid

Streptococcus pneumoniae is a pathogen that causes serious respiratory disease and meningitis in the immunocompromised drug abuse population. However, precise mechanisms by which compromises host immune defense to pulmonary S. infection not fully understood. Using well-established murine model of opiate lung infection, we explored influence morphine treatment on interleukin-23 (IL-23)/IL-17 axis related innate immunity. Impairment early IL-23/IL-17 production caused was associated with delayed neutrophil migration decreased pneumococcal clearance. Furthermore, impaired MyD88-dependent IL-23 alveolar macrophages dendritic cells response vitro cell infection. Moreover, significantly inhibited pneumoniae-induced phosphorylation interferon factor 3 (IRF3), ATF2, NF-kappaBp65. T-cell receptor delta (TCRdelta)-deficient mice showed decrease IL-17 severely weakened capacity clear Finally, resulted diminished secretion antimicrobial proteins S100A9 S100A8/A9 during stages In conclusion, dysfunction IL-23-producing IL-17-producing gammadeltaT lymphocytes This leads release proteins, compromised recruitment, more-severe