title: Dynamics of Salmonella infection of macrophages at the single cell level.
abstract: Salmonella enterica causes a range of diseases. Salmonellae are intracellular parasites of macrophages, and the control of bacteria within these cells is critical to surviving an infection. The dynamics of the bacteria invading, surviving, proliferating in and killing macrophages are central to disease pathogenesis. Fundamentally important parameters, however, such as the cellular infection rate, have not previously been calculated. We used two independent approaches to calculate the macrophage infection rate: mathematical modelling of Salmonella infection experiments, and analysis of real-time video microscopy of infection events. Cells repeatedly encounter salmonellae, with the bacteria often remain associated with the macrophage for more than ten seconds. Once Salmonella encounters a macrophage, the probability of that bacterium infecting the cell is remarkably low: less than 5%. The macrophage population is heterogeneous in terms of its susceptibility to the first infection event. Once infected, a macrophage can undergo further infection events, but these reinfection events occur at a lower rate than that of the primary infection.
authors.affiliation: Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA, UK.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Gog
authors.forename: Alicia
authors.initials: A
authors.lastname: Murcia
authors.forename: Natan
authors.initials: N
authors.lastname: Osterman
authors.forename: Olivier
authors.initials: O
authors.lastname: Restif
authors.forename: Trevelyan J
authors.initials: TJ
authors.lastname: McKinley
authors.forename: Mark
authors.initials: M
authors.lastname: Sheppard
authors.forename: Sarra
authors.initials: S
authors.lastname: Achouri
authors.forename: Bin
authors.initials: B
authors.lastname: Wei
authors.forename: Pietro
authors.initials: P
authors.lastname: Mastroeni
authors.forename: James L N
authors.initials: JL
authors.lastname: Wood
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Maskell
authors.forename: Pietro
authors.initials: P
authors.lastname: Cicuta
authors.forename: Clare E
authors.initials: CE
authors.lastname: Bryant
mesh_terms: D000818:Animals; D002460:Cell Line; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D018715:Microscopy, Video; D018448:Models, Immunological; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology*