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• W86980706 abstract "Candida albicans is a commensal organism in humans, and an importantnopportunistic fungal pathogen. It can cause either mucocutaneous or systemicninfections, both of which are increasing in prevalence, so that C. albicans is now thenfourth leading cause of nosocomial bloodstream infections. Candidiasis usually occursnin patients whose immune defenses have been compromised, but the host response innnormal individuals is not well understood.nnnnnnnnnnnnnnnnnn n Innate immunity is recognized as the first line of defense against Candidaninfection, but cell-mediated immunity is essential for recovery from mucosal infection,nand may play a role in the systemic disease. The position of humoral immunity isnuncertain, though it may have a protective role against systemic infection. However,nlittle is known of the effect of strain variation in C. albicans on susceptibility to Cnalbicans infection in different strains of inbred mice, or of the effects of differentnvirulence phenotypes on the host response. Therefore, this study focused on annanalysis of the following: (1) The effect of infection with different strains of C.nalbicans on the severity of oral and systemic candidiasis in resistant and susceptiblenstrains of inbred mice; (2) A comparison of phagocytosis and killing of differentnstrains of yeasts by neutrophils and macrophages from these mice; (3) The ability ofnantibody to protect against infection, and the spectrum of antigenic determinants tonwhich they respond; (4) The role of T-helper cytokines in candidiasis.nnnnnnnnnnnnnnnnnnnn n Mouse models of systemic and oral candidiasis were established for assessment ofnthe virulence of different strains of yeasts and susceptibility to infection of inbrednmice and cytokine-specific gene knockout mice. Neutrophils and macrophages fromnbone marrow cultures were used for an analysis of phagocytosis and killing of yeasts,nand the effects of opsonisation with normal and immune serum were determined.nWestern blotting was used for the detection of antibody specificity and isotype.nnnnnnnnnnnnnnnnnnn n Of the three strains of C. albicans tested, SC5314 was most virulent in systemicninfection, producing a high fungal burden in the kidney, though it was much lessnefficient in infecting the brain or oral mucosa. Strains 3630 and 3683 establishednconsistent systemic and oral infections, with the latter, an oral isolate, being morenvirulent in oral infection. In the absence of opsonisation, killing by neutrophils fromnmice of both strains was poor, but normal or immune serum dramatically increasednkilling by BALB/c, but not by CBA/CaH cells. Macrophages from BALB/c micenkilled unopsonised yeasts more efficiently than did neutrophils, whereas those fromnCBA/CaH mice were much less effective, except against 3683, which was killednthreefold more efficiently than the other two strains. Opsonisation had no effect on thenkilling of 3683 by either mouse strain, but increased killing of both 3630 and SC5314,nto a greater extent in CBA/CaH than in BALB/c mice. TNF-a, IFN- ƴ and GM-CSFnenhanced the ability of macrophages from CBA/CaH mice to kill yeasts, but had littleneffect on BALB/c macrophages.nnnnnnnnnnnnnnnn n CBA/CaH mice demonstrated a stronger humoral response to Candida infection,nand displayed recognition of a larger range of antigens of C. albicans by both IgGlnand IgG2a, than did BALB/c mice, which produced only IgGl Antigenic profilesntended to be specific for each yeast strain, and this was consistent with a lack ofncross-protection after infection in vivo. An assessment in knockout mice of thenfunctional relevance of various cytokines found that susceptibility to infection wasnaffected neither by IFN- ƴ, IL-4, nor EL-10. In contrast, IL-12 knockout micendeveloped a chronic infection, and macrophages from these mice did not kill yeasts asnefficiently as those from control mice.nnnnnnnnnnnnn n The results confirm the importance of innate immunity in recovery from primaryninfection with C. albicans, but demonstrate significant differences in the ways innwhich phagocytic cells interact with yeasts of different strains. The role of antibodiesnis highly complex, with a marked degree of yeast strain-specificity. Finally, the effectnof cytokines may depend on the genetic context in which the infection occurs.n" @default.
• W86980706 created "2016-06-24" @default.
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• W86980706 date "2005-01-01" @default.
• W86980706 modified "2023-09-23" @default.
• W86980706 title "Murine immune responses to strains of Candida albicans" @default.
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