Search

Mice harbouring a null deletion mutation in the IFNγ receptor gene were used to study the role of IFNγ responsiveness during experimental systemic candidiasis of mucosal or haematogenous origin. After intravenous (i.v.) or intranasal (i.n.) challenge with Candida albicansthe progression of infection and concomitant cellular and antibody anti‐C. albicansimmune responses were analysed. During the week following i.v. challenge, the rate of C. albicansmultiplication in kidneys, liver and spleen was faster in IFNγR (−/−) than IFNγR (+/+) mice. As a result, IFNγR (−/−) mice perished earlier than IFNγR (+/+) mice when challenged with equal numbers of live yeast cells. However, the overall susceptibility of the two mouse strains, in terms of survival against different C. albicanschallenge doses over a 60‐day period, was similar. No differences were found in the cellular anti‐C. albicansresponse generated by i.v. challenge in both mouse strains. In contrast the kinetics and strength of the serum anti‐C. albicansantibody responses were markedly different. Significantly stronger, predominantly IgG2a antibody responses accompanied the eventual control of C. albicansinfection in IFNγR (−/−) mice. Following intranasal challenge, there was no difference in the rate of C. albicansclearance from the lungs of IFNγR (−/−) and IFNγR (+/+) mice. However, 48 h after challenge, large, conspicuous abscesses appeared in the lungs, liver, kidneys and spleen of IFNγR (−/−) mice. These abscesses were characterised by the presence of C. albicansand abundant neutrophilic infiltrates, but very few macrophages. No such abscesses developed in i.n. challenged IFNγR (+/+) mice. In both mouse strains, i.n. challenge induced strong systemic anti‐C. albicanscellular responses, but relatively low titre systemic antibody responses. Mucosal anti‐C. albicansantibody responses were detected in IFNγR (+/+), but not IFNγR (−/−) mice. Splenic adherent macrophages obtained from IFNγR (−/−) mice exhibited a significantly lower candidacidal activity than those of IFNγR (+/+) mice, and as expected, were not responsive to IFNγ. In summary, these data suggest that IFNγ has a role in limiting C. albicansmultiplication during the early stages of infection, as well as in preventing the development of C. albicans‐associated abscesses. Activation of macrophages by IFNγ might be pivotal in mediating this role.

Mice harbouring a null deletion mutation in the IFN? receptor gene were used to study the role of IFN? responsiveness during experimental systemic 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 IFN?R (-/-) than IFN?R (+/+) mice. As a result, IFN?R (-/-) mice perished earlier than IFN?R (+/+) mice when challenged with equal numbers of live yeast cells. However, the overall susceptibility of the two mouse strains, in terms of survival against different C. albicans challenge 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. albicans antibody responses were markedly different. Significantly stronger, predominantly IgG2a antibody responses accompanied the eventual control of C. albicans infection in IFN?R (-/-) mice. Following intranasal challenge, there was no difference in the rate of C. albicans clearance from the lungs of IFN?R (-/-) and IFN?R (+/+) mice. However, 48 h after challenge, large, conspicuous abscesses appeared in the lungs, liver, kidneys and spleen of IFN?R (-/-) mice. These abscesses were characterised by the presence of C. albicans and abundant neutrophilic infiltrates, but very few macrophages. No such abscesses developed in i.n. challenged IFN?R (+/+) mice. In both mouse strains, i.n. challenge induced strong systemic anti-C. albicans cellular responses, but relatively low titre systemic antibody responses. Mucosal anti-C. albicans antibody responses were detected in IFN?R (+/+), but not IFN?R (-/-) mice. Splenic adherent macrophages obtained from IFN?R (-/-) mice exhibited a significantly lower candidacidal activity than those of IFN?R (+/+) mice, and as expected, were not responsive to IFN?. In summary, these data suggest that IFN? 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? might be pivotal in mediating this role.