Immunogenicity and protective effect of recombinant enolase of Candida albicans in a murine model of systemic candidiasis.
Enolase, a 46-kDa glycolytic enzyme, is an immunodominant antigen of the opportunistic pathogen Candida albicans. A recombinant 6 x His-tagged enolase was studied, in conjunction with interleukin-12 (IL-12), as an adjuvant for cytokine induction favouring protection in a murine model of haematogenous candidiasis. Mice immunized with enolase plus IL-12 showed increased antibody titres against enolase, as well as increased median survival time and decreased fungal burden in kidneys, in comparison to non-immunized or IL-12-treated mice. This increased survival was attributable to enolase-induced cell-mediated immunity as it also occurred in B-cell-deficient mice. Enolase immunization stimulated a predominant T-helper-1 (Th1) cytokine pattern in splenic cells and induced production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) by purified CD4+ T cells. However, despite the elevation of immunogenicity, recombinant enolase induced only a modest protection against disseminated candidiasis, suggesting a form of protection likely attributable to the induction of a Th1 cell-mediated immune response.
Laboratory of Bacteriology and Medical Mycology Istituto Superiore di Sanità, Rome, Italy.
Claudia
C
Montagnoli
Silvia
S
Sandini
Angela
A
Bacci
Luigina
L
Romani
Roberto
R
La Valle
D000818:Animals; D000946:Antigens, Fungal / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010751:Phosphopyruvate Hydratase / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D000946:Antigens, Fungal; D016207:Cytokines; D005657:Fungal Vaccines; D011994:Recombinant Proteins; D018664:Interleukin-12; D010751:Phosphopyruvate Hydratase