The interplay between Salmonella typhimurium and its macrophage host--what can it teach us about innate immunity?
Salmonella enterica sv. Typhimurium (S. typhimurium) is a genetically tractable, facultative intracellular pathogen, whose capacity to cause systemic disease in mice depends upon its ability to survive and replicate within macrophages. The identification of Salmonella mutants that lack this activity, has provided a tool with which to dissect the mechanisms used by Salmonella to establish a permissive niche, and identify host activities which it must overcome in order to achieve this. Salmonella actively maintains itself within an intracellular vacuole, thereby shielding itself from an antibacterial activity of host macrophage cytosol. Salmonella controls the maturation of its vacuole, segregating itself from the macrophage degradative pathway. Like several other pathogens, Salmonella reduces the effectiveness of bacteriocidal and bacteriostatic free radicals generated by macrophages, by synthesising enzymes and products that counteract them. Recent evidence indicates that Salmonella also avoids free radical-dependent macrophage antimicrobial mechanisms by more novel means. Here, we review recent studies of the interplay between pathogen and host, with particular emphasis on those areas that suggest new facets to the cell biology of macrophages, and their innate immune functions.
Linehan
Sheena A
SA
The Department of Infectious Diseases, Centre for Molecular Microbiology and Infection, Imperial College of Science, Technology and Medicine, The Flowers Building, Armstrong Road, London SW7 2AZ, UK. s.linehan@ic.ac.uk
Holden
David W
DW
D000818:Animals; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology / Q000502:physiology* / Q000648:ultrastructure; D009154:Mutation; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010088:Oxidoreductases / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012486:Salmonella typhimurium / Q000472:pathogenicity / Q000502:physiology*; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology; D014774:Virulence / Q000276:immunology
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D010088:Oxidoreductases; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II