Effect of Friend leukemia virus infection on susceptibility to Candida albicans

Abstract

Previous studies have demonstrated that Friend leukemia virus (FLV) induces a profound immunosuppression in susceptible mice. The studies described in this report indicate that mice infected with FLV have an increased susceptibility to subsequent infection with the opportunistic pathogen Candida albicans, as measured by increased numbers of C. albicans CFU in the kidneys of FLV-infected mice relative to uninfected controls. Experiments in which the NB-tropic and N-tropic strains of FLV were used suggest that virus replication or the resulting virus burden may be important in the observed increased susceptibility to C. albicans. Since neutrophils are believed to be important in the response of mice to systemic Candida infections, the effect of FLV infection on neutrophil candidacidal activity was investigated. The percentage of neutrophils present in unfractionated Proteose Peptone-elicited peritoneal exudates of mice infected with FLV for 14 days was significantly lower than in uninfected control mice or mice infected with FLV for 6 or 10 days. When neutrophils from FLV-infected and control mice were purified, adjusted to equal concentrations, and tested for in vitro candidacidal activity, neutrophils from mice infected with FLV for 14 days were deficient in their ability to kill C. albicans relative to normal controls and mice infected with FLV for 6 or 10 days. Addition of normal mouse serum increased killing in all groups but did not restore candidacidal activity of neutrophils from mice infected with FLV for 14 days to levels of control neutrophils or neutrophils from mice infected for 6 or 10 days with the virus. These results suggest a defect in neutrophil function, at the later stages of FLV infection, involving in vitro candidacidal activity. In addition, neutrophils from FLV-infected mice may be deficient in in vivo chemotactic activity. These defects in neutrophil function could account, at least in part, for the observed increased susceptibility of FLV-infected mice to C. albicans.

Lipopolysaccharide restores anti-Candida albicans growth inhibition activity of polymorphonuclear neutrophils from retrovirus-immunosuppressed mice

“…By 4 weeks, only limited numbers of PMNs were recovered from the peritoneal cavity. These results were essentially similar to those reported previously (15) and show that migration of PMNs to an inflammatory site may be impaired by infection with FLV.…”

“…For example, various functions of immunologically important cells, including B and T lymphocytes as well as macrophages, are markedly affected after infection of mice with this virus. A recent study by Moors et al demonstrated that impairment of antimicrobial activity of neutrophils also occurs after FLV infection of susceptible mice (15). That is, immune responses to Candida albicans, a ubiquitous opportunistic fungus which causes infections in immunosuppressed individuals, including those with AIDS (19), are depressed in mice infected with FLV and challenged with C. albicans.…”

A role for complement receptor-like molecules in iron acquisition by Candida albicans.

“…COz. C albicans cultured under the above conditions convert from the yeast to the hyphal form in the presence or absence of human serum (26,27). The extent of hyphal growth after 18 h of culture was determined by [3H]glucose uptake assay (26,27) and by MTT assay (28).…”

“…[~H]Glucose Uptake Assay. Assay for Candida hyphal growth by uptake of radiohbded glucose has been described in detail elsewhere (26,27). Briefly, after 18 h of growth under the described experimental conditions, medium was removed, wells were washed with sterile distilled water, and 25 #1 of 2,5[3H]glucose (Net-807, sp act 67 Ci/mMol; New England Nuclear, Boston, MA), diluted to 10 #Ci/ml in sterile water, was added to each well.…”

“…Radioactivity incorporated into C albicans hyphae, which is proportional to the amount of hyphal growth (26,27), was counted in a liquid scintillation counter.…”