Susceptibility of four inbred mouse strains to a low-pathogenic isolate of Yersinia enterocolitica (original) (raw)
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Infection and Immunity
Susceptibility of mice to infection with Yersinia enterocolitica has been shown to be related to neither the Ity locus encoding for resistance to SalmoneUla typhimurium and other pathogens nor the H-2 locus. Recent studies in our laboratory have demonstrated that T-cell-mediated immune responses are required for overcoming primary Yersinia infection. In the present study, we investigated the course of infection with Y. enterocolitica and the resulting immune responses in Yersinia-susceptible BALB/c and Yersinia-resistant C57BL/6 mice. In the early phase of infection, the clearance of the pathogen was comparable in both strains of mice, suggesting similar mechanisms of innate resistance. Splenic T cells from Yersinia-infected C57BL/6 mice exhibited marked proliferative responses and produced gamma interferon (IFN-,y) upon exposure to heat-killed yersiniae. BY contrast, the Yersinia-specific T-cell response in BALB/c mice was weak, and IFN-,y production could not be detected before day 21 postinfection. T cells isolated from C57BL/6 mice 7 days after infection mediated immunity to Y. enterocolitica but those from BALB/c mice did not, while at 21 days postinfection T cells from both strains mediated protection. Neutralization of IFN--y abrogated resistance to yersiniae in C57BL/6 mice but to a far smaller extent in BALB/c mice. Administration of recombinant IFN-'y or anti-interleukin-4 antibodies rendered BALB/c mice resistant to yersiniae, whereas this treatment did not significantly affect the course of the infection in C57BL/6 mice. These results indicate that the cellular immune response, in particular the production of IFN--y by Yersinia-specific T cells, is associated with resistance of mice to Y. enterocolitica. Yersinia enterocolitica is a gram-negative rod-shaped bacterium which is enteropathogenic for humans and rodents (9, 10, 17). Certain mouse strains (BALB/c, C3H/HeN, BALB/b, DBA/2, Swiss, and SWR) are highly susceptible to Y enterocolitica infection (intravenous [i.v.] median lethal dose [LD50J,
Mus spretus SEG/Pas mice resist virulent Yersinia pestis, under multigenic control
Genes and Immunity, 2011
Laboratory mice are well known to be highly susceptible to virulent strains of Yersinia pestis in experimental models of bubonic plague. We have found that Mus spretus-derived SEG/Pas (SEG) mice are exceptionally resistant to virulent CO92 and 6/69 wild type strains. Upon subcutaneous injection of 10 2 colony-forming units (CFU), 90% of females and 68% of males survived, compared with only an 8% survival rate for both male and female C57BL/6 mice. Furthermore, half of the SEG mice survived a challenge of up to 10 7 CFU. The time required for mortality was similar between B6 and SEG, suggesting that survival is dependent on early rather than late processes. The analysis of 322 backcross mice identified three significant quantitative trait loci (QTLs) on chromosomes 3, 4 and 6, with dominant SEG protective alleles. Each QTL increased the survival rate by approximately 20%. The three QTLs function additively, thereby accounting for 67% of the difference between the parental phenotypes. Mice heterozygous for the three QTLs were just as resistant as SEG mice to Y. pestis challenge. The SEG strain therefore offers an invaluable opportunity to unravel mechanisms and underlying genetic factors of resistance against Y. pestis infection.
Immunobiology, 1993
Previous work from this laboratory has demonstrated that cloned T lymphocytes from spleens of Yersinia-infected mice can transfer immunity against Y. enrerocolitica into naive animals. In this study, we investigated the cellular immune response to parenteral infection of Yersinia-resistant C57 BLl6 mice with the highly virulent Y. enrerocolitica strain WA of serotype 0:8 employing immunohistological methods. In the course of the infection the spleen and the liver were the organs most extensively affected. Histologically, three different patterns of inflammatory reactions could be observed: (i) small non-pyogenic granuloma-like lesions (in the liver only), (ii) microabscesses lacking a sharp outline, and (iii) larger abscesses disclosing a distinct cellular border (spleen and liver).
European Journal of Immunology, 1992
The genetic regulation of acute inflammatory reaction (AIR) was studied by the method of bidirectional selective breeding, used to produce a line of mice giving the maximal and a line of mice giving the minimal inflammatory reaction (AIR max and AIR min, respectively). The AIR was triggered by subcutaneous injection of a neutral substrate (suspension of polyacrylamide microbeads), and measured by the leukocyte and serum protein accumulation in the exudate. The two parameters are positively correlated and present a normal frequency distribution. The highly genetically heterogeneous foundation population was produced by the equipoised intercrossing of eight inbred strains of mice, and selective breeding carried out by assortative matings of extreme phenotypes. The response to selection in 11 consecutive generations was highly asymmetrical: a marked AIR increase in the AIR max and no change in the AIR min line occurred.The mean value of realized heritability in the AIR max line was 0.26 and 0.18 for cell and protein concentrations, respectively. The response to selection must have resulted from the interaction of seven to nine independent gene loci endowed with additive effects. The lack of response to selection of the AIR min line is discussed. The large inter-line difference opens new possibilities for studying the biochemistry and molecular genetics of inflammation, and also for investigating the beneficial or detrimental effect of inflammatory responses.
International Immunopharmacology, 2003
The F1 antigen of Yersinia pestis has been identified as one of the protective antigens. The present study aims to generate anti-F1 antibodies in mice of different genetic background and to compare antibody profile, isotype distribution and avidity measurement in sera to observe the pattern of immune response as a strategy to develop F1-based immunogen for plague. The study indicated that, although all the immunological parameters were identical, the avidity of the antibodies was considerably different with various strains of mice. Thus, this study may have an implication while developing F1-based vaccine for plague and avidity measurement definitely has a role for antibody function. D
Characterization of Immune Responses to Yersinia pestis (Indian Isolate) Infection in Mouse Model
Journal of Clinical & Cellular Immunology, 2013
Yersinia pestis, causative agent of plague, is one of the deadliest pathogens around globe. Innate immune response is first line of host defense against pathogens. Here, we have investigated innate and adaptive immune response in plague infected mice, gene expression levels of TLR1-9 and CD14, MyD88, NF-ĸB, TNF-α, MAPKp38, IL-1β were studied in peritoneal macrophages of plague infected mice in a time dependent manner (0 h, 24 h, 48 h, 72 h, 96 h and 120 h of post infection) by qRT-PCR. We also evaluated the immune response to Yersinia outer proteins (Yops) in Y. pestis infected mice. Selected genes (11 numbers) of Y. pestis encoding virulent factors viz, YpkA, YopH, YopM, V antigen, Pla, YopN, YopJ, YopE, YopK, F1 and pH6 antigen were amplified by PCR, cloned and expressed in Escherichia coli. To study the IgG and its isotypes level, ELISA and immunoblotting were performed using purified recombinant antigens. The major antigens recognized by murine plague infected sera were V antigen, YopH, YopM, YopE, F1 but very weak immunoreaction was observed in case of Pla. We observed a significant difference in IgG isotypes (IgG1, IgG2a, IgG2b and IgG3) to V antigen and F1, whereas in case of YopH and YopE (IgG1 and IgG2b) only. We also observed significant increase in the expression of CD14 at 48 h post infection, TLR4 and MyD88 at 72 h post infection in Y. pestis infected mouse peritoneal macrophages. Our findings suggest that both innate and humoral immune responses are crucial for protection.