A MANNOPROTEIN CONSTITUENT OF CANDIDA-ALBICANS THAT ELICITS DIFFERENTLEVELS OF DELAYED-TYPE HYPERSENSITIVITY, CYTOKINE PRODUCTION, AND ANTICANDIDAL PROTECTION IN MICE

To identify major immunogenic constituents of Candida albicans, the ef fect of a mannoprotein fraction (MP-F2) on the elicitation of a delaye d-type hypersensitivity (DTH) reaction, cytokine production, and prote ction from a virulent Candida challenge in a mouse candidiasis model w as studied. In mice immunized with whole cells df a low-virulence stra in 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 typi cal CD4(+) Th2 cytokine. IFN-gamma was produced by CD4(+) cells, and i ts level could be greatly increased by the addition of anti-IL-4 or, m ostly, anti-IL-10 antibodies to the CD4(+) cell cultures. Upon a suita ble schedule of immunization, MP-F2 was also able to induce a vigorous DTH response in Candida-uninfected mice, a response that could be eff iciently transferred into naive recipients by CD4(+) cells from the sp leens of MP-F2-immunized mice. The immunization described above also c onferred 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 wa s as strong as that induced by whole cells, MP-F2-induced protection w as significantly weaker than that conferred by Candida whole-cell immu nization. Mice immunized with either MP-F2 or Candida whole cells had an inverted ratio between the number of CD4(+) splenocytes producing I FN-gamma and that of cells producing IL-4, compared with nonimmunized animals. However, the number of IL-4-producing CD4(+) cells was signif icantly higher in MP-M-vaccinated, weakly protected mice than in Candi da 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 CD 4(+) Th1 and Th2 responses that is so critical in the outcome of host- Candida relationship and are thus potentially relevant in the mechanis ms of Candida-specific DTH regulation and protection.