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PubMed2005

Cancer immunotherapy based on killing of Salmonella-infected tumor cells.

A major obstacle for the development of effective immunotherapy is the ability of tumors to escape the immune system. The possibility to kill tumor cells because they are recognized as infected rather than as malignant could help overcome immune escape mechanisms. Here we report a conceptually new approach of cancer immunotherapy based on in vivo infection of tumors and killing of infected tumor cells. Attenuated but still invasive, Salmonella typhimurium can be successfully exploited to invade melanoma cells that can present antigenic determinants of bacterial origin and become targets for anti-Salmonella-specific T cells. However, to fully appreciate the anticancer therapeutic properties of S. typhimurium, tumor-bearing mice need to be vaccinated against S. typhimurium before intratumoral Salmonella injection. Tumor infection when coupled to anti-Salmonella vaccination leads to 50% to 100% tumor-free mice with a better outcome on larger tumors. Invasive Salmonella also exert an indirect toxic effect on tumor cells through the recruitment of inflammatory cells and the cross-presentation of tumor antigens, which allow induction of tumor-specific immune response. This is effective in retarding the growth of untreated established distant tumors and in protecting the mice from subsequent tumor challenges.

Animals↗
PubMed1975

Salmonella infections in Stockholm. A 10-year review.

During the 10-year period 1963-1972 the total number of cases of salmonella infection reported to the Public Health Administration in Stockholm was 3012. The annual incidence varied between 72 (1966) and 23 (1972) per 100000 population. Peak frequencies appeared in the age groups 15-25 and 45-64 years. 101 different serotypes were diagnosed with S. typhi murium being the most common type (37%). 63% of the cases were infected during travel to foreign countries and in 19% food-borne transmission occurred. During the 6-year period 1963-1968 85% of all cases were treated in hospitals. In 1969 a new law governing infectious diseases came into force making it easier to reduce the strict measures imposed by the previous law of 1919. During the 4-year period 1969-1972 53% of the cases were hospitalized. In spite of this reduction no change in the annual pattern of secondary cases has been observed.

Adolescent↗
PubMed1988

Salmonella infections in infants in Hawaii.

In a 10-year cohort of 117 infants hospitalized in Honolulu with Salmonella infections, there were 12 infants with bacteremia or complications (simple bacteremia, 7; bacteremia with probably unrelated concurrent infection, 2; serious complications, 3). The rate of serious complications in this cohort was low and occurred only in infants with previous chronic illness or clinically obvious extraintestinal infection at the time of presentation. Antibiotics were not shown to be of benefit in reducing the frequency of complications; however, the sample size was too small to make definitive conclusions. These data do not support the contention that infants with Salmonella gastroenteritis are at increased risk of complications and should therefore be treated with antibiotics. Rather, the same clinical risk factors for sepsis that apply to all infants also apply to infants with Salmonella gastroenteritis and the decision to begin antibiotic treatment should be based on similar clinical information.

Anti-Bacterial Agents↗
PubMed1995

Effects of in vivo administration of anti-IL-10 monoclonal antibody on the host defence mechanism against murine Salmonella infection.

Interleukin-10 (IL-10) is a cytokine that regulates various macrophage functions. To elucidate the involvement of endogenous IL-10 in the early stage of murine salmonellosis, we examined the effect of anti-IL-10 monoclonal antibody (mAb) administration on the host defence mechanism against Salmonella choleraesuis infection. The in vivo administration of anti-IL-10 mAb significantly enhanced host resistance at the early stage of Salmonella infection, as assessed by bacterial growth in the peritoneal cavity and the liver. Enhanced levels of monokine mRNA, including IL-1 alpha, tumour necrosis factor-alpha (TNF-alpha) and IL-12, were observed from day 1 after infection in the peritoneal macrophages in anti-IL-10 mAb-treated mice compared with those in control mAb-treated mice. Mice treated with anti-IL-10 mAb exhibited significantly higher levels of interferon-gamma (IFN-gamma) in the peritoneal exudates and major histocompatibility complex (MHC) class II expression on the peritoneal macrophages on days 3 and 5 after infection. Notably, in vivo anti-IL-10 mAb brought about an increment of gamma delta T cells in the peritoneal cavity at the early phase of infection, which was correlated with the expression of endogenous heat-shock protein 60 (HSP60), which is implicated as a potential ligand for gamma delta T cells, in the infected macrophages. Our results suggest that the neutralization of endogenous IL-10 accelerates some macrophage functions and, consequently, the activation of immunocompetent cells, including gamma delta T cells, at the early stage of infection, resulting in an enhanced host defence against Salmonella infection.

Animals↗
PubMed2001

Effect of Salmonella-infected human monocytes on natural killer cell cytotoxicity. In vitro studies.

Various chemicals, including some bacteria-derived components, modulate natural killer cell (NKC) activity. We have analyzed the effect of wild-type Ty2 and of mutant strain TYT1231 Salmonella typhi-infected monocytes (U937 cells and human autologous monocytes) on NKC cytotoxicity of peripheral blood mononuclear cell (PBMC) and highly purified NKC (HPNKC; CD16+/56+ > 95%; the rest corresponding to CD3+ T-cells). PBMC's co-culture with either S. typhi strain infected U937 cells (medium or non-infected U937 cells as controls) resulted in the induction of lymphocyte activated killer (LAK) cell activity showing cytotoxicity against target human NKC-resistant lymphoblastoid Daudi cell line. Comparable experiments using autologous monocytes gave similar results. Co-culture of HPNKC preparations with either S. typhi strain infected U937 cells resulted in increased LAK cell activity against target Daudi cells in each and everyone of the five samples tested; paired Student's t-test p < 0.01 for both times (20 and 40 h) tested. Similar to the results observed in the experiments using PBMC, we did not find significant differences in the ability between medium and non-infected cells, or between wild-type S. typhi Ty2 and mutant strain TYT1231 infected U937 cells, to induce LAK activity in HPNKC preparations. PBMC co-incubation with either S. typhi strain infected U937 cells or autologous monocytes resulted in significant increases in IL-12, TNF-alpha, and IFN-gamma secretion. In similar experiments using HPNKC samples instead, infected U937 cells significantly increased IL-12 and IFN-gamma, but not TNF-alpha secretion. PBMC co-incubation with non-infected U937 cells, but not with non-infected monocytes, significantly increased supernatant IL-12 and TNF-alpha levels (no significant changes in IFN-gamma were recorded). Secreted cytokines remained essentially unchanged after co-incubating HPNKC preparation with non-infected U-937 cells. Incubation of PBMC or HPNKC preparations with either S. typhi strain infected U937 cells failed to produce significant changes in the expression of NKC lineage (CD16+/56+) or activation (CD28+, CD69+ and CD95+) markers. The ability of infected monocytes to induce LAK activity, release NKC cytokines and upmodulate NKC's CD95+ marker expression was essentially the same for both infecting Salmonella strains used. These results suggest a role for NKC in the physiological defensive response against intracellularly infected monocytes representing, perhaps one of the earliest antimicrobial mechanisms of the innate immune system.

Acid Phosphatase↗
PubMed1995

[Model for experimental efficacy testing of control measures against Salmonella infections in poultry].

An infection model is shown for testing the efficacy of prophylactic and therapeutic measures against S. typhimurium and S. enteritidis infections of chickens at different ages. By detecting viable counts in caecum and liver or spleen respectively at weekly intervals after administration of salmonellas (crop instillation) the course of salmonella infection can be grasped. Oral application of the salmonella strains used (S. typhimurium and S. enteritidis) to 1-day-old chickens at a dose of 10(2) cfu/bird, to 8-days-old chickens at a dose of 10(9) cfu/bird and to 5-weeks-old chickens at a dose of 10(10) cfu/bird resulted in a characteristic course of infection but not in clinical symptoms or death. By detecting viable counts of the challenge strain in the organs testing the efficacy of a preceding immunization is possible.

Aging↗
PubMed1994

Host specificity of Salmonella infection in chickens and mice is expressed in vivo primarily at the level of the reticuloendothelial system.

By experimental infection, host-specific Salmonella serotypes were shown to demonstrate specificities for chickens, mice, and other laboratory animals. Following oral inoculation, four strains of Salmonella gallinarum and two S. pullorum strains, isolated from diseased poultry, were more virulent for chickens than for mice. By contrast, four strains each of S. choleraesuis and S. dublin, isolated from diseased pigs and cattle, respectively, were more virulent for mice than for chickens. These results were also reflected in the degree of virulence expressed after parenteral inoculation. In addition, S. choleraesuis, but not other serotypes, killed rats, guinea pigs, and rabbits. S. typhimurium strains varied widely in their virulence, and some strains were virulent for both mice and chickens. Four other serotypes isolated from poultry or human food poisoning cases and a nonpathogenic Escherichia coli strain were much less virulent for both experimental host species. Most of the host-specific Salmonella serotypes studied were able to colonize the distal alimentary tract and invade the tissues in both mice and chickens to various degrees. There was, however, a greater difference in the ability to survive and multiply in the visceral organs, particularly the spleen and the liver, once invasion had occurred which correlated with the virulence for the host species involved.

Animals↗
PubMed1987

Salmonella infections of the urinary tract.

Infection of the urinary tract is a relatively rare manifestation of salmonellosis, most often seen in elderly and debilitated patients. The literature is reviewed briefly with a focus on the mechanisms whereby the urinary tract may be involved in salmonellosis, i.e. ascending or haematogenous invasion of the urinary tract. Predisposing factors, clinical course, and recommendations for follow-up of patients are commented on. Ten cases of urinary tract infections caused by various Salmonellae illustrate the nosology.

Adult↗
PubMed1981

The anaerobically cultured cecal flora of adult fowls that protects chickens from Salmonella infections.

In this work we have analyzed the bacterial composition of anaerobically cultured cecal contents (mixed broth culture) of adult fowls previously shown able to protect 1 day old chickens from oral Salmonella infections. All four cultures studied in this paper gave complete protection against Salmonella infantis when used undiluted or in the 10(-2) dilution and at least some protection in the 10(-4) dilution. The total aerobic as well as anaerobic counts on the nonselective medium used (VLMH) were of the order of 10(8) viable organisms/ml indicating that the mixed broth culture consisted predominantly of facultative organisms. From a total of 239 colonies isolated on the basis of colony morphology 66 were obligate anaerobes and 173 facultative anaerobic or microaerophilic species. Isolates were selected from each medium. They were grouped and tentatively classified on the basis of their ability to grow on selective media, their colony and cell morphology. Gram stain and products formed from glucose fermentation (obligate anaerobes). Further characterization was performed using conventional carbohydrate fermentation and biochemical tests. However only a minor fraction of the anaerobic isolates could be identified as being identical to known species. The most numerous species were E. coli and various Lactobacilli which were still found in the highest dilution (10(-8)) of the broths. Fecal streptococci were the next most frequent, isolated at the 10(-7) dilution. The obligate anaerobes isolated included Gram-positive cocci and Gram-positive and -negative rods tentatively classified as Eubacteria, Propionibacteria, Clostridia, Fusobacteria and Bacteroides. A large number of them were isolated from the 10(-6) dilution and some species of Eubacteria and Clostridia could only be recovered from the 10(-3) or 10(-4) dilutions.

Anaerobiosis↗