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.
Jensen
J
J
Department of Surgery, University of Wisconsin Medical School, Madison 53706-1532.
Vazquez-Torres
A
A
Balish
E
E
D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000276:immunology*; D005767:Gastrointestinal Diseases / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology; D007372:Interferons / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D010587:Phagocytosis; D011070:Poly I-C / Q000494:pharmacology*
D007370:Interferon Type I; D007371:Interferon-gamma; D007372:Interferons; D011070:Poly I-C