POLY(I.C)-INDUCED INTERFERONS ENHANCE SUSCEPTIBILITY OF SCID MICE TO SYSTEMIC CANDIDIASIS

In the absence of any demonstrable T- or B-cell responses, gnotobiotic CB-17 SCID (severe combined immunodeficient) mice not only show innate resistance to acute systemic (intravenous challenge) candidiasis but also manifest innate resistance to systemic candidiasis of endogenous (gastrointestinal tract) origin. Poly(I . C), a potent inducer of interferons (IFNs) in vivo, enhanced the susceptibility of CB-17 SCID mice to acute systemic candidiasis and to systemic candidiasis of endogenous origin, as demonstrated by increased numbers of viable Candida albicans in internal organs after poly(I . C) treatment. The poly(I . C)-enhanced susceptibility of mice to candidiasis was abrogated by in vivo treatment with antibodies to IFN-alpha, -beta, and -gamma. In vivo depletion of natural killer cells from SCID mice did not significantly enhance their susceptibility to systemic candidiasis or abrogate poly(I . C)-enhanced susceptibility. In vivo and in vitro, treatment with poly(I . C) impaired the candidacidal and phagocytic activity of thioglycollate-elicited macrophages from SCID mice. Antibody to IFN-alpha/beta or IFN-beta alone interfered with the ability of poly(I . C) to impair the candidacidal activity of macrophages from SCID mice in vitro. These data suggest that poly(I . C)-induced interferons can impair the candidacidal activity of macrophages in SCID mice and decrease their innate resistance to acute systemic candidiasis and to systemic candidiasis of endogenous origin.