Characterisation of Candida albicans infections of haematogenous and mucosal origin in mice lacking the interferon gamma receptor protein

Mice harbouring a null deletion mutation in the IFN gamma receptor gene wer e used to study the role of IFN gamma responsiveness during: experimental s ystemic candidiasis of mucosal or haematogenous origin. After intravenous ( i.v.) or intranasal (i.n.) challenge with Candida albicans the progression of infection and concomitant cellular and antibody anti-C. albicans immune responses were analysed. During the week following i.v, challenge, the rate of C, albicans multiplication in kidneys, liver and spleen was faster in I FN gamma R (-/-) than IFN gamma R (+/+) mice. As a result. IFN gamma R (-/- ) mice perished earlier than IFN gamma R (+/+) mice when challenged with eq ual numbers of live yeast cells. However. the overall susceptibility of the two mouse strains, in terms of survival against different C. albicans chal lenge doses over a 60-day period, was similar. No differences were found in the cellular anti-C. albicans response generated by i.v, challenge in both mouse strains. In contrast the kinetics and strength of the serum anti-C a lbicans antibody responses were markedly different. Significantly stronger, predominantly IgG2a antibody responses accompanied the eventual control of C. albicans infection in IFN gamma R (-/-) mice. Following intranasal chal lenge, there was no difference in the rate of C. albicans clearance from th e lungs of IFN gamma R (-/-) and IFN gamma R (+/+) mice. However, 48 h afte r challenge, large, conspicuous abscesses appeared in the lungs, liver, kid neys and spleen of IFN gamma R (-/-) mice. These abscesses were characteris ed by the presence of C, albicans and abundant neutrophilic infiltrates, bu t very few macrophages. No such abscesses developed in i.n. challenged IFN gamma R (+/+) mice. In both mouse strains, i.n. challenge induced strong sy stemic anti-C. albicans cellular responses, but relatively low titre system ic antibody responses. Mucosal anti-C. albicans antibody responses were det ected in IFN gamma R (+/+). but not IFN gamma R (-/-) mice. Splenic adheren t macrophages obtained from IFN gamma R (-/-) mice exhibited a significantl y lower candidacidal activity than those of IFN gamma R (+/+) mice, and as expected, were not responsive to IFN gamma. In summary, these data suggest that IFN gamma has a role in limiting C, albicans multiplication during the early stages of infection: as well as in preventing the development of C. albicans-associated abscesses. Activation of macrophages by IFN gamma, migh t be pivotal in mediating this role. (C) 2000 Federation of European Microb iological Societies. Published by Elsevier Science B.V. All rights reserved .