Dissociation of innate susceptibility to Salmonella infection and endotoxin responsiveness in C3HeB/FeJ mice and other strains in the C3H lineage

Eisenstein, Toby K.; Deakins, L. W.; Killar, Loran M.; Saluk, Paul H.; Sultzer, Barnet M.

doi:10.1128/iai.36.2.696-703.1982

Cited by 46 publications

(16 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Research using mouse typhoid infections has supported this view. Different C3H lineage mice, either unresponsive or highly susceptible to the toxic effects of injected LPS, died with equivalent lethal loads of salmonellae (Eisenstein et al, 1982), arguing against a role for endotoxin in causing death in salmonellosis. This view was also endorsed by Collins (1979).…”

Section: Discussionmentioning

confidence: 99%

A lethal role for lipid A in Salmonella infections

Khan

Everest

Servos

et al. 1998

Molecular Microbiology

200

176

View full text Add to dashboard Cite

SummarySalmonella infections in naturally susceptible mice grow rapidly, with death occurring only after bacterial numbers in vivo have reached a high threshold level, commonly called the lethal load. Despite much speculation, no direct evidence has been available to substantiate a role for any candidate bacterial components in causing death. One of the most likely candidates for the lethal toxin in salmonellosis is endotoxin, specifically the lipid A domain of the lipopolysaccharide (LPS) molecule. Consequently, we have constructed a Salmonella mutant with a deletion-insertion in its waaN gene, which encodes the enzyme that catalyses one of the two secondary acylation reactions that complete lipid A biosynthesis. The mutant biosynthesizes a lipid A molecule lacking a single fatty acyl chain and is consequently less able to induce cytokine and inducible nitric oxide synthase (iNOS) responses both in vivo and in vitro. The mutant bacteria appear healthy, are not sensitive to increased growth temperature and synthesize a full-length Oantigen-containing LPS molecule lacking only the expected secondary acyl chain. On intravenous inoculation into susceptible BALB/c mice, wild-type salmonellae grew at the expected rate of approximately 10-fold per day in livers and spleens and caused the death of the infected mice when lethal loads of approximately 10 8 were attained in these organs. Somewhat unexpectedly, waaN mutant bacteria grew at exactly the same rate as wild-type bacteria in BALB/c mice but, when counts reached 10 8 per organ, mice infected with mutant bacteria survived. Bacterial growth continued until unprecedentedly high counts of 10 9 per organ were attained, when approximately 10% of the mice died. Most of the animals carrying these high bacterial loads survived, and the bacteria were slowly cleared from the organs. These experiments provide the first direct evidence that death in a mouse typhoid infection is directly dependent on the toxicity of lipid A and suggest that this may be mediated via proinflammatory cytokine and/or iNOS responses.

show abstract

Section: Discussionmentioning

confidence: 99%

A lethal role for lipid A in Salmonella infections

Khan

Everest

Servos

et al. 1998

Molecular Microbiology

200

176

View full text Add to dashboard Cite

show abstract

“…On the other hand, the M ¤ inflammatory response is crucial to control S. typhimurium infections, since the M ¤ -depleted mice were not able to control the infection. Indeed, it has been shown that mice which have a genetic defect in the lps gene and which are therefore hyporesponsive to the biological effects of LPS, are not able to control S. typhimurium infections [31]. Certainly, additional experiments involving the measurement of inflammatory cytokines during S. typhimurium infection in M ¤ -depleted mice are warranted to provide more insight into how the M ¤ -Salmonella interaction initiates pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Dual role for macrophages in vivo in pathogenesis and control of murine Salmonella enterica var. Typhimurium infections

et al. 2000

View full text Add to dashboard Cite

Salmonella spp. are regarded as facultative intracellular bacterial pathogens which are found inside macrophages (M ¤ ) after i. v. infection. It is generally assumed that M ¤ restrict the replication of the bacteria during infection. In this study we examined the in vivo activities of M ¤ during experimental S. typhimurium infections, using a selective liposome-based M ¤ elimination technique. Unexpectedly, elimination of M ¤ prior to infection with virulent S. typhimurium decreased morbidity and mortality, suggesting that M ¤ mediate the pathology caused by S. typhimurium. Removal of M ¤ during vaccination with attenuated S. typhimurium did not affect protection against challenge with virulent S. typhimurium, suggesting that M ¤ are not required for the induction of protective immunity and that other cells must function as antigen-presenting cell to elicit T cell-mediated protection. However, M ¤ appeared to be important effectors of protection against challenge infection since elimination of M ¤ from vaccinated mice prior to challenge infection with virulent S. typhimurium significantly decreased protection. These results enhance our understanding of the control of S. typhimurium growth in vivo, and moreover suggest that M ¤ play a major role in the pathology of virulent S. typhimurium infections. As such, these cells may present a novel target for therapeutic intervention.

show abstract

“…The innate susceptibility or resistance of mice to S. typhimurium infection is governed by several genes (13,27,(45)(46)(47), and differences in the genetic background between nonresponder and responder mouse strains may contribute to this heterogeneity through the growth and/or elimination rate of S. typhimurium. For instance, we showed that following i.p.…”

Section: Discussionmentioning

confidence: 99%

Control by H-2 genes of the Th1 response induced against a foreign antigen expressed by attenuated Salmonella typhimurium

et al. 1996

View full text Add to dashboard Cite

Attenuated salmonellae represent an attractive vehicle for the delivery of heterologous protective antigens to the immune system. Here, we have investigated the influence of the genetic background of the host which regulates the growth and elimination of Salmonella cells on the cellular response induced against a foreign antigen delivered by an aroA Salmonella strain. We have tested CD4 ؉ T-cell responses (cell proliferation and cytokine production) in various mouse strains following immunization with Salmonella typhimurium SL3261 expressing a high level of the recombinant Escherichia coli MalE protein. We were able to detect a CD4 ؉ T-cell response against the recombinant MalE protein only in a restricted number of mouse strains, whereas all mice produced good levels of anti-MalE immunoglobulin G antibodies. The Ity gene did not play a major role in these differences in T-cell responses, since both Ity-resistant and -susceptible strains of mice were found to be unresponsive to MalE delivered by recombinant salmonellae. In contrast, when B10 congenic mice were used, a correlation was established between MalE-specific T-cell unresponsiveness and H-2 genes. The discrepancies described in this paper in the ability of various strains of mice to develop an efficient Th1 response against a recombinant antigen displayed by a live Salmonella vaccine underscore the difficulties that can be encountered in the vaccination of human populations by such a strategy.

show abstract

Dissociation of innate susceptibility to Salmonella infection and endotoxin responsiveness in C3HeB/FeJ mice and other strains in the C3H lineage

Cited by 46 publications

References 28 publications

A lethal role for lipid A in Salmonella infections

A lethal role for lipid A in Salmonella infections

Dual role for macrophages in vivo in pathogenesis and control of murine Salmonella enterica var. Typhimurium infections

Control by H-2 genes of the Th1 response induced against a foreign antigen expressed by attenuated Salmonella typhimurium

Contact Info

Product

Resources

About