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The involvement of tumor necrosis factor in immunity to Salmonella infection
J P Tite1, G Dougan, S N Chatfield
1Department of Molecular Biology, Wellcome Biotech, Beckenham, Kent, UK.
Abstract:
The role of TNF in immunity to Salmonella in mice was studied. Antiserum specific for murine TNF was raised and used to neutralize TNF activity in vivo. Injection of this serum into mice infected with the moderately mouse virulent Salmonella typhimurium strain M525 caused exacerbation of disease. Such treatment had no effect on the course of an infection with an attenuated S. typhimurium aroA (strain SL3261) mutant. However, the protection afforded by immunisation with live SL3261 against challenge with the virulent parent strain (SL1344) was abolished by anti-TNF antiserum. Interestingly both early (3 wk) immunity and late (10 wk) immunity was neutralized by such treatment. Inasmuch as early immunity is considered to be nonspecific and macrophage-mediated while late immunity is considered to be serotype-specific and T cell mediated, this suggests that TNF plays a role in protection from Salmonellosis in both cases.
Insights
Tumor necrosis factor (TNF) plays a crucial role in controlling Salmonella infections in mice. Neutralizing TNF exacerbates disease and abolishes protective immunity, highlighting its importance in host defense against Salmonellosis.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Salmonella typhimurium is a significant bacterial pathogen causing Salmonellosis.
- Tumor necrosis factor (TNF) is a key cytokine involved in immune responses.
- The specific role of TNF in Salmonella immunity requires further elucidation.
Purpose of the Study:
- To investigate the role of TNF in the host immune response to Salmonella infection in a murine model.
- To determine if TNF neutralization affects disease severity and protective immunity.
Main Methods:
- Development of specific antiserum to neutralize murine TNF activity in vivo.
- Infection of mice with virulent (Salmonella typhimurium M525) and attenuated (S. typhimurium aroA SL3261) Salmonella strains.
- Administration of anti-TNF antiserum to assess its impact on infection course and vaccine-induced immunity.
Main Results:
- Neutralization of TNF activity exacerbated disease in mice infected with virulent Salmonella.
- Anti-TNF treatment did not affect infection with an attenuated Salmonella strain.
- Protection conferred by immunization with live attenuated Salmonella against virulent challenge was abolished by anti-TNF antiserum.
- Both early (macrophage-mediated) and late (T cell-mediated) immunity were abrogated by TNF neutralization.
Conclusions:
- TNF is essential for effective immunity against Salmonella in mice.
- TNF plays a critical role in both non-specific and specific immune responses to Salmonella infection.
- Targeting TNF could be a potential therapeutic strategy for Salmonellosis.