title: Dynamics of Increasing IFN-γ Exposure on Murine MH-S Cell-Line Alveolar Macrophage Phagocytosis of Streptococcus pneumoniae.
abstract: Previous investigations have demonstrated that activation with the type II interferon, IFN-γ, downregulates alveolar macrophage (AM) phagocytosis of Streptococcus pneumoniae. While these studies have shown clear effects at discrete time points, the kinetics of the macrophage response to IFN-γ over time, with respect to pneumococcal phagocytosis, have not been shown. Here, we describe these kinetics in the murine MH-S AM cell-line, a well-established model useful for investigations of AM phenotype and function. We measure binding and internalizing rates of S. pneumoniae following exposure to increasing durations of physiologic levels of IFN-γ. When MH-S murine alveolar macrophage (mAM) were exposed to IFN-γ for increasing durations of time, from 0 to 6 days before inoculation with the type II S. pneumoniae, D39, exposure for 6 h transiently reduced bacterial binding by 50%, which was temporarily restored at 2 and 3 days of exposure. Bacterial internalization was also reduced shortly following initial exposure, however, internalization continued to fall to less than 5% that of IFN-γ naïve controls after 6 days of exposure. These data may help explain otherwise contradictory reports from the literature regarding timing between infections and reductions in macrophage function.
authors.affiliation: 1 Medical Scientist Training Program, Emory University School of Medicine , Atlanta, Georgia .|2 Hubert Department of Global Health, Rollins School of Public Health, Emory University , Atlanta, Georgia .|3 Department of Pediatrics, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mina
authors.affiliation: 3 Department of Pediatrics, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Lou Ann S
authors.initials: LA
authors.lastname: Brown
authors.affiliation: 2 Hubert Department of Global Health, Rollins School of Public Health, Emory University , Atlanta, Georgia .
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
mesh_terms: D000818:Animals; D002460:Cell Line; D007371:Interferon-gamma / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology*; D013997:Time Factors
chemical_list: D007371:Interferon-gamma