Protective immunity induced by low-virulence Candida albicans: cytokine production in the development of the anti-infectious state.
A low-virulence, agerminative strain of Candida albicans (PCA-2) is able to confer a high degree of nonspecific protection against subsequent challenge with highly virulent microorganisms in mice. In an attempt to better define the effect of PCA-2 vaccination on the immune system and the nature of the mechanisms involved in this protective state, we evaluated the pattern and kinetics of production of selected cytokines in PCA-2-treated mice. Thus, granulocyte/monocyte colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 1 (IL-1) were measured in the sera and spleen cell supernatants of vaccinated mice. In both cases, high levels of CSF, TNF, IL-1, and IFN were found 6 hr after PCA-2 infection and persisted for many days. There was always a correlation between the ability of PCA-2 to induce antimicrobial protection in vivo and its ability to cause cytokine production in vitro. Supernatants of splenocyte cultures from PCA-2-infected animals possessed macrophage-activating activity, as measured in microbiological assays. These data suggest an important involvement of cytokines in the nonspecific anti-infectious immunity induced by PCA-2, and also suggest a crucial role for IL-1 as an endogenous adjuvant in the initiation of the immune response to PCA-2.
Vecchiarelli
A
A
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Cenci
E
E
Puliti
M
M
Blasi
E
E
Puccetti
P
P
Cassone
A
A
Bistoni
F
F
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000096:biosynthesis*; D002176:Candida albicans / Q000276:immunology* / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology / Q000517:prevention & control*; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D016207:Cytokines; D004306:Dose-Response Relationship, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D008262:Macrophage Activation; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014611:Vaccination
D001685:Biological Factors; D003115:Colony-Stimulating Factors; D016207:Cytokines; D006133:Growth Substances; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D000666:Amphotericin B; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor