A mannoprotein constituent of Candida albicans that elicits different levels of delayed-type hypersensitivity, cytokine production, and anticandidal protection in mice.
To identify major immunogenic constituents of Candida albicans, the effect of a mannoprotein fraction (MP-F2) on the elicitation of a delayed-type hypersensitivity (DTH) reaction, cytokine production, and protection from a virulent Candida challenge in a mouse candidiasis model was studied. In mice immunized with whole cells of a low-virulence strain of C. albicans and thus protected against a challenge with a highly virulent strain of this fungus, MP-F2 was able to elicit a strong DTH response that was accompanied by splenocyte proliferation in vitro in the presence of Candida antigen. The supernatants of MP-F2-stimulated splenocyte cultures contained gamma interferon (IFN-gamma, a typical CD4+ T helper-1 (Th1) cytokine, but no interleukin-4, (IL-4), a typical CD4+ Th2 cytokine. IFN-gamma was produced by CD4+ cells, and its level could be greatly increased by the addition of anti-IL-4 or, mostly, anti-IL-10 antibodies to the CD4+ cell cultures. Upon a suitable schedule of immunization, MP-F2 was also able to induce a vigorous DTH response in Candida-uninfected mice, a response that could be efficiently transferred into naive recipients by CD4+ cells from the spleens of MP-F2-immunized mice. The immunization described above also conferred to mice a low degree of protection against a virulent Candida challenge, both in terms of median survival time and in the number of Candida cells in the kidney. However, while DTH induction by MP-F2 was as strong as that induced by whole cells, MP-F2-induced protection was significantly weaker than that conferred by Candida whole-cell immunization. Mice immunized with either MP-F2 or Candida whole cells had an inverted ratio between the number of CD4+ splenocytes producing IFN-gamma and that of cells producing IL-4, compared with nonimmunized animals. However, the number of IL-4-producing CD4+ cells was significantly higher in MP-F2-vaccinated, weakly protected mice than in Candida whole-cell-vaccinated, highly protected animals. Overall, our data suggest that the MP-F2 fraction contains one or more major immunogens of C. albicans which are capable of interfering with the balance of CD4+ Th1 and Th2 responses that is so critical in the outcome of host-Candida relationship and are thus potentially relevant in the mechanisms of Candida-specific DTH regulation and protection.
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
A
A
Mencacci
A
A
Torosantucci
R
R
Spaccapelo
L
L
Romani
F
F
Bistoni
A
A
Cassone
D000818:Animals; D000946:Antigens, Fungal / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002177:Candidiasis / Q000276:immunology / Q000517:prevention & control*; D002478:Cells, Cultured; D002678:Chimera; D016207:Cytokines / Q000096:biosynthesis; D005656:Fungal Proteins / Q000627:therapeutic use*; D006183:H-2 Antigens / Q000235:genetics; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D016233:Immunotherapy, Active; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007668:Kidney / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D016019:Survival Analysis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000946:Antigens, Fungal; D016207:Cytokines; D005656:Fungal Proteins; D006183:H-2 Antigens; D008562:Membrane Glycoproteins; C025363:mannoproteins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma