Enhanced resistance against systemic Candida albicans infection in mice treated with C. albicans DNA.

In this study, double-stranded Candida albicans DNA was administered in systemic C. albicans infection in at dose of 20 microg per mouse at 4, 5 and 6 weeks of age. The level of IL-12 in serum was elevated as a result of yeast DNA treatment and correlated with lower mortality and decreased kidney and liver injury. Macrophage activation was demonstrated by an increase of nitric oxide (NO) and IL-12 production. These effects were Janus activation kinases (JAK)/signal transducer and activator of transcription (STAT) dependent as they were inhibited by selective JAK inhibitor tyrphostin AG-490. DNA influenced adaptive immune response through elevation of anti-Candida IgG antibody production in systemic C. albicans infection. Thus, C. albicans DNA augmented innate and adaptive immune responses against the pathogen.

Candida albicans double-stranded DNA can participate in the host defense against disseminated candidiasis.

In the present work, we studied the in vitro immunomodulatory properties of double-stranded Candida albicans DNA and its protective effect in murine disseminated candidiasis. DNA induced the production of TNF-alpha by peritoneal macrophages and splenocytes in vitro through a chloroquine-dependent mechanism. Yeast DNA acted synergistically with IFN-gamma in triggering the secretion of nitric oxide by macrophages and enabled them to stimulate the proliferation of T cells in response to soluble anti-CD3. The effect of DNA on splenocytes is associated with an enhanced synthesis of IFN-gamma, IL-2 and IL-10. In vivo, DNA decreased the mortality and lowered the kidney contamination in mice intraperitoneally inoculated with C. albicans simultaneously with an increase in the specific proliferative response and cytokine production. The present results indicate that C. albicans DNA can provide protection against disseminated infection.

Inflammation induced by inoculation of the joint with Candida albicans.

In humans Candida albicans is the most frequently isolated opportunistic fungal pathogen. In immunocompromized host the balance with the commensal fungus easily turns to life-threatening disseminated infection. The asymptomatic Candida persistence in organs and the recurrent infections suggest continuous circulation of yeast cells and their degradation products. Under certain conditions, joints might become one of the infectious sites. More easily a reactivation and destructive process can be provoked in individuals with established arthritis. We have investigated the joint inflammation caused by inoculation of the paw with live C. albicans, in intact mice and mice with collagen-induced arthritis (CIA). The results demonstrate that C. albicans infection when localized into the joints caused rapidly progressing septic arthritis. The effect was associated with a strong swelling, a rapid influx of polymorphonuclear (PMN) cells, and an elevated secretion of TNF-alpha and IFN-gamma by lymph node cells. Joint infection exacerbated the established CIA which correlated with an increased level of anti-collagen antibodies.

Antiarthritic effect of VIP in relation to the host resistance against Candida albicans infection.

Vasoactive intestinal peptide (VIP) is one of the prospective candidates for clinical application in rheumatoid arthritis (RA). Its antiarthritic effect is associated with the suppression of inflammatory and autoimmune responses. The ability of VIP to trigger a shift towards Th2 immunity suggests that anti-infectious host resistance might be affected. In the present study VIP was applied at the initiation and at the established phase of collagen-induced arthritis (CIA). Mice developed Th2 dominant anti-collagen response. The susceptibility to primary and secondary Candida albicans infection was determined after VIP administration at the established CIA. The percentage of survivors, kidney colonization, cytokine secretion by splenocytes and specific antibody synthesis were assessed. Reduced TNF-alpha production but not IFN-gamma and IL-10 was observed after the first challenge with the pathogen in CIA mice treated with VIP while the percentage of survivors was not significantly changed. The adaptive immune response was impaired in VIP-treated mice as they were more susceptible to reinfection, showed increased kidney colonization and suppressed anti-Candida IgG antibody production.

Single immunization of newborn mice with heterologous type-II collagen induces arthritic disease.

Collagen-induced arthritis (CIA) is a widely accepted model of autoimmune disease with significant similarities to rheumatoid arthritis in humans. CIA is provoked in susceptible strains upon immunization of adult mice with native type-II collagen in complete Freund's adjuvant (CFA). Neonatal exposure to antigen is supposed to result in T cell clone deletion and induction of tolerance. Here we report that the neonatal injection of bovine type-II collagen (bCII) to ICR (CD-2) mice triggers the development of autoimmune chronic joint inflammation. Compared with standard CIA significant joint swelling was not observed and anti-collagen antibodies were not detected if the second challenge with the antigen was not supplied. Histopathologic examination of the joints showed cell infiltration, synovial hyperplasia and at the later period bone destruction. Mice immunized as neonates expressed Ag-specific proliferative response and delayed type hypersensitivity (DTH) reaction to bCII.

Host resistance against Candida alibcans infection in mice with adjuvant induced arthritis.

In mice and humans two distinct CD4+ helper T cells, known as Th1 and Th2 are identified. They are characterized by the different cytokine milleau they induce. The balance between Th1 and Th2 responses is thought to be decisive for the initiation and course of some autoimmune disorders, as well as for the outcome of infectious processes. In the present study the development of Candida alibcans infection in mice with adjuvant-induced arthritis was investigated. An impaired host resistance against C. alibcans in arthritic mice was registered when the inoculation was done during the early and the established phases of arthritis. In contrast, the slight elevation of the number of survivors was detected when the infection was induced at the peak of inflammation. These data correlated with the changes of serum TNF-alpha level and delayed type hypersensitivity (DTH) to C. alibcans.