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Peripheral blood granulocytes and mononuclear cell responses in monkeys with experimental shigellosis
Abstract:
Changes in neutrophil response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the phenotype of peripheral blood mononuclear cells were studied in monkeys after oral challenge with Shigellae. Monkeys were first challenged with S. dysenteriae 1 which caused shigellosis in some of the monkeys. After recovery, the monkeys were rechallenged with S. flexneri 2a. No difference in sensitivity was observed in the monkeys during shigellosis caused by either S. dysenteriae 1 or S. flexneri 2a. The optimal dose of FMLP for neutrophil polarization, a measure of early cell activation, in normal healthy monkeys was 10(-7) M when 67% of the neutrophils were polarized. Neutrophils from monkeys ill with shigellosis required higher doses of FMLP (10(-6) and 5 x 10(-7) M) for maximum polarization. As the monkeys recovered, a gradual decrease in the doses of FMLP for optimal neutrophil polarization was also observed. The percentage of CD2-positive T lymphocytes, the earliest marker for T lymphocytes in the peripheral blood, decreased when the monkeys developed shigellosis and returned to normal levels as the monkeys improved. However, there was no change in the percentage of CD20-positive peripheral blood B lymphocytes.
Insights
Shigellosis alters immune cell function, requiring higher FMLP doses for neutrophil activation and decreasing T lymphocytes during illness. Immune responses normalize as monkeys recover from Shigella infection.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Shigellosis, a severe diarrheal disease, is caused by Shigella bacteria.
- Understanding the host immune response is crucial for managing Shigella infections.
Purpose of the Study:
- To investigate changes in neutrophil function and peripheral blood mononuclear cell phenotype during Shigella infection in a primate model.
- To assess the impact of Shigella dysenteriae 1 and Shigella flexneri 2a challenges on immune cell responses.
Main Methods:
- Monkeys were orally challenged with Shigella species.
- Neutrophil polarization in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was measured.
- Flow cytometry was used to analyze the phenotype of peripheral blood mononuclear cells, including CD2-positive T lymphocytes and CD20-positive B lymphocytes.
Main Results:
- Neutrophils from sick monkeys required higher FMLP concentrations for optimal polarization compared to healthy controls.
- Neutrophil polarization response improved as monkeys recovered.
- A decrease in CD2-positive T lymphocytes was observed during shigellosis, with levels returning to normal upon recovery.
- No significant changes were noted in CD20-positive B lymphocytes.
Conclusions:
- Shigellosis impairs neutrophil activation and reduces circulating T lymphocytes in a primate model.
- These immune alterations are reversible and correlate with disease progression and recovery.
- The study highlights specific cellular immune changes associated with Shigella infection.