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Protective capacity of L-form Salmonella typhimurium against murine typhoid in C3H/HeJ mice
F Nishikawa1, E Kita, H Yamada
1Department of Bacteriology, Nara Medical University, Japan.
Abstract:
L forms of Salmonella typhimurium LT2 conferred strong protection to a lethal challenge with its parental bacterium on innately hypersusceptible C3H/HeJ mice, and its minimal protective dose was approximately 150 L-forming units. Although L-form S. typhimurium was avirulent for C3H/HeJ mice, it multiplied slowly in both the liver and spleen with the maximal growth 2-3 weeks after immunization and thereafter it persisted in the liver until 24 weeks. Protective immunity began to work between 4 and 6 weeks after immunization, and it remained active as long as the L forms colonized the liver (until 24 weeks after immunization). Vaccination with the L form induced a population of T cells responding to L-form whole-cell lysate (WCL), while delayed-type hypersensitivity (DTH) to the extract of S. typhimurium was induced after the establishment of solid immunity. Moreover, neither T-cell responses nor DTH to heat-killed S. typhimurium was generated. In addition, antibody responses were elicited to WCL but not to heat-killed S. typhimurium. These results indicate that protection conferred by the L forms is attributable to the persistent colonization of the L forms rather than the presence of DTH, and also that Salmonella cytoplasmic antigens are involved in induction of immunological responses by vaccination with the L forms.
Insights
L forms of Salmonella typhimurium LT2 provide strong protection against lethal challenges in mice. This immunity is linked to persistent L-form colonization, not delayed-type hypersensitivity, involving Salmonella cytoplasmic antigens.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Salmonella typhimurium L forms are cell-wall deficient bacterial variants.
- C3H/HeJ mice are innately hypersusceptible to Salmonella infections.
- Understanding novel vaccine strategies against Salmonella is crucial.
Purpose of the Study:
- To evaluate the protective efficacy of Salmonella typhimurium L forms as a vaccine.
- To investigate the immunological mechanisms underlying L-form-induced protection.
- To determine the role of Salmonella cytoplasmic antigens in immune responses.
Main Methods:
- Immunization of C3H/HeJ mice with live L forms of Salmonella typhimurium LT2.
- Assessment of protection against a lethal challenge with parental S. typhimurium.
- Monitoring of L-form colonization in the liver and spleen.
- Evaluation of T-cell responses, delayed-type hypersensitivity (DTH), and antibody production.
Main Results:
- L forms conferred strong protection at a minimal dose of 150 L-forming units.
- L forms were avirulent but persisted in the liver and spleen for up to 24 weeks.
- Protective immunity developed between 4-6 weeks post-immunization and correlated with L-form colonization.
- T-cell and antibody responses were elicited against L-form whole-cell lysate (WCL), but not heat-killed S. typhimurium.
- DTH responses were induced late, after solid immunity was established.
Conclusions:
- Persistent colonization by L forms of Salmonella typhimurium is responsible for protective immunity.
- Salmonella cytoplasmic antigens, present in WCL, are involved in inducing protective immune responses.
- L-form vaccination offers a promising alternative strategy for Salmonella control, distinct from traditional methods.