GAMMA-INTERFERON IS NOT ESSENTIAL IN HOST-DEFENSE AGAINST DISSEMINATED CANDIDIASIS IN MICE

In vitro studies have suggested a role for interferon gamma (IFN-gamma ) in host defense against disseminated candidiasis, but in vivo studie s are inconclusive. We utilized homozygous IFN-gamma knockout (GKO) mi ce to determine if the cytokine is essential in host defense against t his disease, Genotypes of mice were determined by PCR with specific pr imers for the normal or disrupted IFN-gamma gene, The GKO status of th e mice was confirmed by an enzyme-linked immunosorbent assay, which sh owed no detectable IFN-gamma produced by their splenocytes stimulated by concanavalin A. To test the susceptibility of GKO mice to candidias is, the animals were infected either intravenously (i.v.) or intragast rically (i.g.) with Candida albicans. GKO mice infected i.v. survived as long as wild-type (WT) mice and showed no difference in Candida CFU counts in liver, spleen, or kidneys compared to those for WT mice. Wh en animals were given Candida i.g., at 3 h or at 10 or 21 days after i nfection, there was no dissemination of Candida to the lung, liver, sp leen, or kidneys far either GKO or WT mice. There was no difference in Candida CFU counts recovered from the stomach or intestines between G KO and WT mice, Histological examination of the stomach cardial-atrium fold, where the fungus was located, showed that GKO mice did not have evidence of more tissue damage or fungal invasion than WT mice, Final ly, the jejunum for both types of mice showed no evidence of tissue da mage or fungal invasion, These studies indicate that IFN-gamma is not essential in host defense against C. albicans that originates from a m ucosal site or that is given directly into the bloodstream in a mouse model.