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Oxygen-independent antimicrobial activity against Salmonella enteritidis of specially activated macrophage with
T Sasahara1, N Ikewaki, H Tamauchi
1Department of Microbiology, Kitasato University School of Medicine, Kanagawa, Japan.
Abstract:
Characteristics of peritoneal macrophages recovered from mice infected with two attenuated strains SER and Jena of Salmonella enteritidis were compared. Strong resistance against lethal infection with a virulent strain 116-54 of S. enteritidis was seen in a group of mice immunized with strain SER, but not in a group of mice immunized with strain Jena as well as in a control group. Peritoneal macrophages from mice immunized with strain SER showed an enhanced Salmonella-killing activity, an increased generation of O2- and an increased expression of Ia antigen on 7 to 14 days after infection when compared with those from mice immunized with strain Jena and thioglycollate(TG)-elicited macrophages as a control. The bacterial number of strain Jena in organs decreased more rapidly than that of strain SER after day 4 of infection. These observations suggest that the survival of an attenuated Salmonella bacilli at reticulo-endothelium is essential to increase of their activities of macrophages. Macrophages from mice injected with recombinant interferon(IFN)-gamma for 3 days induced the activated stage of the same characteristics as noted in activated macrophages from mice immunized with strain SER. Effect of oxygen intermediates (OI) scavengers such as superoxide dismutase and catalase on Salmonella-killing activity of activated macrophages was not seen at all. These results suggest that an increased generation of OI may be not primarily responsible for the ability to inhibit the intracellular growth of a virulent strain of S. enteritidis in macrophages activated by immunization with live, attenuated strains and injection with rIFN-gamma.
Insights
Immunization with the attenuated Salmonella enteritidis SER strain enhances macrophage activity and Salmonella resistance. This suggests attenuated bacterial survival in the host is key for boosting macrophage function against virulent strains.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Salmonella enteritidis infections pose significant health risks.
- Understanding macrophage activation is crucial for developing effective immune responses.
- Attenuated bacterial strains are explored for their potential in immunotherapy.
Purpose of the Study:
- To compare the characteristics of peritoneal macrophages from mice infected with two attenuated Salmonella enteritidis strains (SER and Jena).
- To investigate the protective immunity conferred by immunization with these attenuated strains against virulent Salmonella.
- To elucidate the role of macrophage activation and oxygen intermediates in combating Salmonella infection.
Main Methods:
- Comparison of peritoneal macrophage activity in mice immunized with attenuated Salmonella strains (SER, Jena) and controls.
- Assessment of Salmonella-killing activity, oxygen radical generation, and Ia antigen expression in macrophages.
- Evaluation of bacterial load in organs post-infection.
- Investigation of the effects of recombinant interferon-gamma (IFN-γ) and oxygen intermediate scavengers on macrophage function.
Main Results:
- Mice immunized with SER strain showed strong resistance to virulent Salmonella, unlike those immunized with Jena or controls.
- SER-immunized macrophages exhibited enhanced Salmonella-killing activity, increased O2- generation, and higher Ia antigen expression.
- Bacterial clearance was more rapid in mice infected with strain Jena compared to SER after day 4.
- Recombinant IFN-γ induced macrophage activation similar to that seen with SER immunization.
- Oxygen intermediate scavengers did not affect the Salmonella-killing activity of activated macrophages.
Conclusions:
- Survival of attenuated Salmonella within the reticuloendothelial system is essential for enhancing macrophage activity.
- Macrophage activation by attenuated Salmonella strains or IFN-γ plays a key role in controlling virulent Salmonella infection.
- Increased oxygen intermediate generation may not be the primary mechanism for inhibiting intracellular virulent Salmonella growth in activated macrophages.