Tumor Necrosis Factor Alpha Receptor I Is Important for Survival from Streptococcus pneumoniae Infections (original) (raw)
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Bali Medical Journal
Background: Pneumococci cause mild or severe infections that begin with colonization in the nasopharyngeal area. Intranasal transmission is a natural route of bacterial infection in the host. This study aims to determine the type of serotype that can infect and provide an overview of inflammation in the lungs of mice after exposure to 107 bacteria S. pneumoniae serotypes 2, 3, 4, 19F and ATCC 6030 intranasally in animals try Balb / c mice. Methods: True experimental study was conducted using Randomized Posttest Only Control Group Design among 30 Balb/c mice divided into 3 groups. The intervention used in this study was carried out twice, namely at 24 hours and 48 hours with 50 μl suspension of Streptococcus pneumoniae bacterial inoculum via intranasal drop by drop. Lung histopathology and CFU analysis of infected mice were evaluated. TNF-α was examined using ELISA. Data were analyzed using SPSS software version 17 for windows. Results: The results showed that S. pneumoniae serotype 3 could infect Balb / c mice and found about 5x104 CFU (SD ± 7x104 CFU) at 101 dilutions and was still detected at 104 dilutions i.e. 0.5 CFU (SD ± 0.7 CFU) at 24 hours post-infection as well at 48 hours postinfection, accompanied by infiltration of neutrophil cells in the lung tissue at the same time. The TNF-α levels did not significantly differ between the treatment group (P>0.05) Conclusion: The results of this study indicate that not all S. pneumoniae serotypes can infect experimental animals.
Roumanian archives of microbiology and immunology
Animal models of infection and protection on the topic of the Streptococcus pneumoniae (S. pneumoniae) have encountered many difficulties generated by low immunogenicity, a characteristic of polysaccharide capsular bacteria and difference of virulence between serotypes and strains. We have explored the immune response after immunization with heat inactivated S. pneumoniae serotype 1, 3 and 6B in C57BL/6 mice by IgM and IgG detection, and by splenocyte in vitro 5-ethynyl-2'-deoxyuridine (EdU) incorporation after antigen specific stimulation, as a proposed method of cellular immune response evaluation. Antibody titer persistence after immunization was not lengthy while antigen specific proliferation response detected by EdU assay was remnant. Intraperitoneal (i.p.) challenge with serotype 6B S. pneumoniae proved that antibody titers and the detected specific cellular immune response do not cover seroprotective necessity and do not confer improved immunologic memory in comparison t...
FEMS Microbiology Letters, 2003
Gram-negative enteric bacilli are agents of life-threatening pneumonia. The role of the bacterial capsule and O-antigen moiety of lipopolysaccharide in the pathogenesis of Gram-negative pneumonia was assessed. In a rat model of pneumonia the LD 50 of a wild-type extraintestinal pathogenic Escherichia coli strain (CP9) was significantly less than its isogenic derivatives deficient in capsule (CP9.137), O-antigen (CP921) or both capsule and O-antigen (CP923) (P 9 0.003). Studies using complement depleted or neutropenic animals established that both neutrophils and complement are important for the pulmonary clearance of E. coli. Data from these studies also support that capsule and O-antigen serve, at least in part, to counter the complement and neutrophil components of the pulmonary host defense response. Lastly, the contribution of E. coli versus neutrophils in causing lung injury was examined. Findings suggest that E. coli virulence factors and/or non-neutrophil host factors are more important mediators of lung injury than neutrophils. These findings extend our understanding of Gram-negative pneumonia and have treatment implications.
Infection and Immunity
Cytokines are suspected of playing an important role in the pathophysiology of septic shock. This study was undertaken to determine whether tumor necrosis factor alpha (TNF-a) induces the production of other cytokines and mediates mortality in a neonatal rat model of sepsis caused by group B streptococci (GBS). We have measured TNF-a, interleukin-la (IL-1a), interleukin-6 (IL-6), and gamma interferon (IFN-y) levels in neonatal rats infected with different strains (H738, 259, and 90) and doses (1 50% lethal dose [LD50] and 5 90% lethal doses [LD,0]) of type III GBS. TNF-ca and IL-6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial plasma samples. IL-la and IFN-y were measured in spleen homogenates by enzyme-linked immunosorbent assay kits by using antibodies raised against the corresponding mouse cytokines. Plasma TNF-a levels significantly rose above baseline values within 12 h after intraperitoneal challenge with 5 LD90 of GBS strain H738, corresponding to 3 x 103 CFU. A mean peak TNF-a concentration of 232 + 124 U/ml was reached at 20 h. Peak IL-la and IL-6 levels of 766 404 U/g and 1,033 + 520 U/ml, respectively, were reached at 24 h after bacterial challenge. Maximal spleen concentrations of IFN-y (449 283 U/g) were measured at 36 h. Concentrations of TNF-a, but not other cytokines, remained significantly elevated at 72 h, a time when mortality approached 100%o. Significant correlations were found between concentrations of each of the cytokines tested and the logs of CFU concentrations in the blood. In order to ascertain whether TNF-a influenced the production of other cytokines, rat pups received two in,jections of anti-murine TNF-a or normal rabbit serum at 2 h before and at 26 h after challenge with live GBS. Plasma TNF-a bioactivity was undetectable in anti-TNF-a-treated animals, while IL-6 and IFN-y, but not IL-1a, levels were significantly reduced, compared with normal serum controls. Rat pups pretreated with anti-TNF-a serum and infected with 1 and 5 LD90 of strains H738 and 259 showed enhanced early (48 to 72 h) survival.
Australian Journal of Experimental Biology and Medical Science, 1985
Elicited, mouse peritoneal exudate cells were fractionated by centrifugation on discontinuous Percoll density gradients. TVo subpopulations of neutrophils, each of greater than 90% purity, were isolated at discontinuous density gradient interfaces different from the region of mononuclear ceU enrichment (i.e., 1-0694-1 0871 and 1-0872-1-1002 g/ml for neutrophils and less than 1-0694 g/ml for mononuclear cells). Peritoneal exudate cells were mixed with Proteus mirabitis in the presence of 1% normal mouse serum for 30 min. The mixtures were fractionated on gradients of Percoll diluted with a clacium-free medium. Populations of cells banding at densities greater than 1-0693 g/ml were washed free of gradient material, and neutrophil suspensions containing intracellular bacteria and which were relatively free of extracellular bacteria were isolated. Less than 7% of the total bacteria present was extracellular. The continuing extracellular presence of a heat-labile component of normal mouse serum was essential for maximal intracellular kill of P. mirabitis by mouse peritoneal neutrophils.
Protection against Pneumococcal Pneumonia in Mice by Monoclonal Antibodies to Pneumolysin
Infection and Immunity, 2004
We examined the ability of three murine monoclonal antibodies (MAbs) to PLY (PLY-4, PLY-5, and PLY-7) to affect the course of pneumococcal pneumonia in mice. The intravenous administration of antibodies PLY-4 and PLY-7 protected the mice from the lethal effect of the purified toxin. Mice treated with PLY-4 before intranasal inoculation of S. pneumoniae type 2 survived longer (median survival time, 100 h) than did untreated animals (median survival time, 60 h) (P < 0.0001). The median survival time for mice treated with a combination of PLY-4 and PLY-7 was 130 h, significantly longer than that for mice given isotype-matched indifferent MAbs (P ؍ 0.0288) or nontreated mice (P ؍ 0.0002). The median survival time for mice treated with a combination of three MAbs was significantly longer (>480 h) than that for mice treated with PLY-5 (48 h; P < 0.0001), PLY-7 (78 h; P ؍ 0.0007), or PLY-4 (100 h; P ؍ 0.0443) alone. Similarly, the survival rate for mice treated with three MAbs (10 of 20 mice) was significantly higher than the survival rate obtained with PLY-5 (1 of 20; P ؍ 0.0033), PLY-4 (2 of 20; P ؍ 0.0138), or PLY-7 (3 of 20; P ؍ 0.0407) alone. These results suggest that anti-PLY MAbs act with a synergistic effect. Furthermore, MAb administration was associated with a significant decrease in bacterial lung colonization and lower frequencies of bacteremia and tissue injury with respect to the results for the control groups.