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Diminished neutrophil oxidative metabolism after phagocytosis of virulent Salmonella typhi
Abstract:
The interactions of human polymorphonuclear neutrophils (PMNs) with virulent and avirulent strains of Salmonella typhi were examined. Ingestion of the S. typhi strains by PMNs was evaluated with three techniques: visual examination of PMN monolayers (phagocytic index); uptake of radiolabeled S. typhi by PMNs; and removal of S. typhi from the supernatant of suspensions of PMNs and bacteria. All three techniques indicated equivalent phagocytosis of the strains. Postphagocytic PMN oxidative metabolism was quantitated with measurements of oxygen consumption, protein iodination, and chemiluminescence. We found that although PMNs ingested equal numbers of virulent and avirulent S. typhi, those PMNs ingesting the virulent organisms exhibited a significantly smaller increase in postphagocytic oxidative metabolism than PMNs ingesting avirulent S. typhi. Despite this muted oxidative burst the virulent bacteria were killed as well as the avirulent strains. Virulent S. typhi either fail to stimulate receptors that trigger PMN oxidative metabolism or inhibit PMN oxidative metabolism. Our data support the former hypothesis.
Insights
Human neutrophils (PMNs) ingest virulent and avirulent Salmonella typhi equally. However, virulent bacteria trigger a weaker oxidative burst in PMNs, suggesting they may evade immune detection by not stimulating key receptors.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Human polymorphonuclear neutrophils (PMNs) are critical immune cells involved in phagocytosing and killing bacterial pathogens.
- Salmonella typhi is the causative agent of typhoid fever, a significant global health concern.
- Understanding bacterial evasion mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the differential interactions between human PMNs and virulent versus avirulent strains of Salmonella typhi.
- To determine if bacterial virulence affects PMN phagocytosis and post-phagocytic oxidative metabolism.
- To elucidate potential mechanisms by which virulent S. typhi may evade the host immune response.
Main Methods:
- Quantified phagocytosis using three methods: visual assessment (phagocytic index), radiolabeled bacteria uptake, and bacterial clearance from supernatant.
- Assessed PMN oxidative metabolism post-ingestion by measuring oxygen consumption, protein iodination, and chemiluminescence.
- Compared the responses of PMNs exposed to virulent and avirulent S. typhi strains.
Main Results:
- All methods confirmed equivalent phagocytosis of both virulent and avirulent S. typhi by PMNs.
- PMNs ingesting virulent S. typhi exhibited significantly reduced post-phagocytic oxidative metabolism compared to those ingesting avirulent strains.
- Despite the muted oxidative burst, virulent S. typhi were killed as effectively as avirulent strains.
Conclusions:
- Virulent S. typhi appear to evade the PMN oxidative burst, likely by failing to stimulate the receptors that initiate this crucial immune response.
- This immune evasion mechanism may contribute to the pathogenesis of typhoid fever.
- Further research is needed to confirm the specific receptors involved in this interaction.