Acquired resistance to Cryptococcus neoformans in adult mice vaccinated as newborns

Although Cryptococcus neoformans causes serious infections in AIDS patients, cryptococcosis in immunologically immature infants, as in immunocompetent adults, is rare. To investigate the resistance of neonates to C. neoformans and to determine, whether they could be efficiently vaccinated as neonates against challenge with the yeast as adults, the course of infection was monitored in the lungs of mice infected intranasally with yeast cells, Neonates were less able than adults to reduce yeast burdens less than 24 h postinoculation and less able to control the progressive growth of yeast over several weeks, However, in both neonates and adults, yeasts were substantially eradicated ba. 6 to 8 weeks after infection, Numbers of all classes of leukocytes recovered from Lung lavages of infected neonates and adults were similar, Significant differences appeared only on day 14, when neonates had more neutrophils and adults had significantly more CD4(+) CD45RB cells with low fluorescence intensity, When vaccinated neonates were rechallenged after reaching adulthood, they expressed resistance to e. neoformans as efficiently as did mice immunized as adults and survived an intravenous challenge that was lethal for unimmunized controls, Thus, exposure of neonatal mire to viable C. neoformans yeast, which persists in the lungs for mana weeks, does not result in immunological tolerance to a yeast challenge in adult mice! as predicted by immunological dogma, but instead immunizes them, Therefore, even in immunologically immature individuals, the immune system sen es to protect against pathogens rather than simply to distinguish self from nonself.