Role of natural killer cells in resistance to Cryptococcus neoformans infections in mice

Abstract

Previous studies have suggested a possible role for natural killer (NK) cells in resistance to some fungal infections, including Cryptococcus neoformans infections. The role of NK cells in early clearance of C neoformans from tissues and in long-term survival was studied in mice following intravenous inoculations of the organism. Mice treated with anti-asialo GM1 antiserum to temporarily reduce NK activity demonstrated an increase in colony-forming units (CFU) of C neoformans in the lung 24 hours after an intravenous inoculation of the organism. CFU in liver, spleen, kidney, and brain were not different in anti-asialo GM1 antiserum-treated versus control mice. An NK-specific reagent, anti-NK 1.1 monoclonal antibody, was used to deplete mice of NK cells in vivo for at least 14 days without affecting other natural defenses. The number of C neoformans retained in the lungs 24 hours after inoculation of the organism was significantly greater in NK cell-depleted mice than in controls, although CFU in other organs were unaffected. Following the intravenous inoculation of C neoformans, the survival of anti-NK 1.1-treated mice was not different from control mice. The effect of NK cell activity on resistance to C neoformans was also determined after an intratracheal inoculation of the organism. Mice pretreated with anti-NK 1.1 demonstrated no increases in CFU in the lungs, spleen, or brain as compared with controls. These data indicate that NK cells can play a role in vivo in early resistance against C neoformans if the organism is delivered via the intravenous route. However, NK cells do not play a role in either determining survival after an intravenous inoculation nor in resistance during an infection acquired via the respiratory tract.