Related Experiment Videos
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.
Insights
Natural killer (NK) cells aid early Cryptococcus neoformans clearance in mouse lungs after intravenous infection. However, NK cells do not influence long-term survival or resistance to respiratory fungal infections.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Natural killer (NK) cells are implicated in host defense against fungal pathogens.
- Cryptococcus neoformans is an opportunistic fungal pathogen causing severe infections.
- The specific role of NK cells in C. neoformans infection dynamics requires further elucidation.
Purpose of the Study:
- To investigate the role of NK cells in early Cryptococcus neoformans clearance from tissues.
- To determine the impact of NK cell activity on survival following C. neoformans infection.
- To assess NK cell function in response to different routes of C. neoformans inoculation.
Main Methods:
- Mice were treated with anti-asialo GM1 antiserum or anti-NK 1.1 monoclonal antibody to deplete NK cells.
- Colony-forming units (CFU) of C. neoformans were quantified in various organs post-intravenous (IV) or intratracheal (IT) inoculation.
- Survival rates were monitored in NK cell-depleted mice following IV C. neoformans challenge.
Main Results:
- Temporary NK cell reduction increased C. neoformans CFU in lungs 24 hours post-IV inoculation.
- NK cell depletion using anti-NK 1.1 antibody resulted in higher lung CFU post-IV challenge but did not affect survival.
- NK cells did not influence C. neoformans CFU in other organs or resistance following IT inoculation.
Conclusions:
- NK cells contribute to early-phase resistance against C. neoformans, specifically following intravenous administration.
- NK cells do not appear to be critical for long-term survival or defense against respiratory C. neoformans infections.
- The route of pathogen entry significantly influences the role of NK cells in C. neoformans pathogenesis.