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The interplay between Salmonella typhimurium and its macrophage host--what can it teach us about innate immunity?
Sheena A Linehan1, David W Holden
1The 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
Abstract:
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.
Insights
Salmonella Typhimurium evades macrophage defenses by controlling its vacuole and counteracting free radicals. This review explores novel mechanisms of Salmonella survival within host macrophages and innate immunity.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Salmonella Typhimurium is a facultative intracellular pathogen causing systemic disease in mice.
- Its virulence depends on survival and replication within macrophages.
- Understanding Salmonella's interaction with macrophages is key to dissecting host-pathogen mechanisms.
Purpose of the Study:
- Review recent studies on Salmonella-macrophage interplay.
- Highlight mechanisms Salmonella uses to establish a permissive intracellular niche.
- Identify host activities Salmonella must overcome for survival.
Main Methods:
- Review of existing literature on Salmonella Typhimurium pathogenesis.
- Analysis of studies focusing on Salmonella's intracellular survival strategies.
- Examination of macrophage innate immune responses to Salmonella.
Main Results:
- Salmonella maintains itself in a vacuole, avoiding macrophage cytosol.
- The pathogen actively controls vacuole maturation, evading degradation.
- Salmonella synthesizes compounds to counteract macrophage-generated free radicals, employing novel avoidance strategies.
Conclusions:
- Salmonella employs sophisticated mechanisms to survive within macrophages.
- These mechanisms involve vacuolar control and free radical neutralization.
- Further research into these interactions reveals new aspects of macrophage cell biology and innate immunity.