ABSTRACT
A mouse model of Helicobacter pylori infection was used to evaluate the vaccine antigen potential of the citrate synthase homologue protein purified from the H. pylori NCTC 11637 strain. Mice were immunised with the protein by intra-Peyer's patch immunisation. This route gives maximal intestinal immunisation and was used to screen oral vaccine candidate antigens without the added complication of simultaneously testing oral delivery systems. Two weeks post-immunisation mice were infected with Sydney strain H. pylori and 4 weeks after infection the mice were killed and the level of H. pylori infection in the stomach determined. Pre-immunisation with the 50/52-kDa protein led to a 84-91% reduction in H. pylori infection compared to unimmunised controls.
Subject(s)
Bacterial Vaccines/immunology , Citrate (si)-Synthase/immunology , Helicobacter Infections/prevention & control , Peyer's Patches/immunology , Animals , Antigens, Bacterial/immunology , Antigens, Bacterial/isolation & purification , Bacterial Vaccines/administration & dosage , Citrate (si)-Synthase/chemistry , Disease Models, Animal , Electrophoresis, Polyacrylamide Gel , Female , Helicobacter Infections/microbiology , Helicobacter pylori/enzymology , Helicobacter pylori/immunology , Helicobacter pylori/isolation & purification , Mice , Mice, Inbred C57BLSubject(s)
Candidiasis, Vulvovaginal/genetics , Genetic Predisposition to Disease , Haplotypes , Major Histocompatibility Complex/genetics , Animals , Antibodies, Fungal/analysis , Antigens, Fungal/immunology , Candidiasis, Vulvovaginal/pathology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Mice , Mice, Inbred Strains , Specific Pathogen-Free Organisms , Vagina/microbiology , Vagina/pathologyABSTRACT
The role of the host immune system in combating candidal infections in the vagina is poorly understood. A murine model of Candida vaginitis was used to elucidate the role of T cells in a candidal infection. Athymic BALB/c nu/nu mice or normal BALB/c mice were induced into estrus and then infected with 1 x 10(6) Candida albicans intravaginally. The infection was monitored over 1 week. Samples from blood, small intestine, tongue, kidney, spleen, liver, uterus and vagina were tested for recoverable C. albicans. Histology of the vagina was assessed for both inflammation and extent of infection. Results indicated that the BALB/c nu/nu mice had similar levels of vaginal yeast load to the normal BALB/c mice. In 25-30% of nude mice Candida was also recovered from extra vaginal sites (kidney, liver, small intestine), however, extra vaginal dissemination was not observed in any normal BALB/c animals. Histologically, both the nu/nu and control BALB/c had similar levels of vaginal inflammation; however, the nu/nu mice had more florid fungal growth in the vaginal epithelium. Adoptive transfer of either immune or non-immune BALB/c T cells into nude mice had no affect on either infection or vaginal inflammation. Immunohistochemical staining of vaginal tissues from normal BALB/c mice or nude mice adoptively transferred with either immune or non-immune T cells with anti-CD3 monoclonal antibody revealed no significant difference between groups in the numbers of CD3+ vaginal T cells. However, in mice receiving either immune or non-immune T cells no yeast was recovered from any tissues except the vagina. These data show that T cells have a limited role in protecting the vagina from C. albicans infection.
Subject(s)
Candidiasis, Vulvovaginal/prevention & control , Immunologic Deficiency Syndromes/therapy , Immunotherapy, Adoptive , Mice, Nude/immunology , T-Lymphocytes/transplantation , Animals , Candida albicans/isolation & purification , Candidiasis, Vulvovaginal/etiology , Candidiasis, Vulvovaginal/immunology , Candidiasis, Vulvovaginal/microbiology , Candidiasis, Vulvovaginal/pathology , Disease Models, Animal , Epithelial Cells/immunology , Epithelial Cells/microbiology , Estradiol/pharmacology , Estrus , Female , Fungemia/etiology , Fungemia/immunology , Fungemia/therapy , Genetic Predisposition to Disease , Immunity, Cellular , Immunologic Deficiency Syndromes/complications , Interleukin-3/metabolism , Mice , Mice, Inbred BALB C , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Vagina/immunology , Vagina/microbiology , Vagina/pathologyABSTRACT
Impaired T cell function has been reported to predispose women to recurrent vulvovaginal candidiasis, but conflicting results have been noted in the literature. Most clinical episodes occur in the late luteal phase, suggesting hormonal influence on host resistance. The present study assesses the cellular immune responses of 28 women with recurrent vaginal candidiasis (patients) and 25 control women (controls), noting results in relation to whether the women were in the follicular or luteal phase of the menstrual cycle at the time of sampling. Candida-stimulated peripheral blood lymphocyte proliferation was significantly reduced in patients compared with controls. Interferon-gamma (IFN-gamma) production in response to both Candida and purified protein derivative (PPD) stimulation was significantly lower in patients compared with controls. Skin test responses were comparable in both groups. A significant reduction in Candida-stimulated IFN-gamma production was seen in patients but not controls in the follicular phase compared with those in the luteal phase. There was also a trend towards lower proliferation in response to Candida in patients but not controls in the follicular phase compared with patients in the luteal phase. These results suggest that there is a partial T cell dysregulation in recurrent vaginal candidiasis which may be exacerbated by the hormonal balance present during the follicular phase, correlating with the risk of clinical infection.
Subject(s)
Candidiasis, Vulvovaginal/immunology , Adult , Antigens, Fungal/immunology , Antigens, Fungal/pharmacology , Candida/immunology , Candidiasis, Vulvovaginal/blood , Cytokines/biosynthesis , Female , Follicular Phase/physiology , Humans , Hypersensitivity, Delayed/immunology , Immunity, Cellular/immunology , Luteal Phase/physiology , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Middle Aged , Phytohemagglutinins/pharmacology , T-Lymphocytes/immunologyABSTRACT
We have used a mouse model of vaginal candidiasis to determine the effect of neutrophil depletion on (a) the clearance of Candida albicans and (b) the degree of inflammation associated with infection. No differences in recoverable yeast number or rate of clearance were observed between normal and neutrophil-depleted mice; however, vaginal inflammation was significantly decreased in neutrophil-depleted animals.