Acquired immunity in experimental murine aspergillosis is mediated by macrophages. Infect

A number of studies have substantiated the pivotal role of innate defense mechanisms in protection against invasive aspergillosis. However, experiments demonstrating increased resistance to lethal intravenous (i.v.) infection with Aspergillusfumigatus conidia in cortisone-treated or untreated mice preinfected with a sublethal dose of conidia and protection of turkeys inoculated subcutaneously with a killed A.fiumigatus germling vaccine against subsequent aerosol challenge led us to speculate that acquired immunity may also contribute to host defense against Aspergilus infection. Five-week-old male BALB/c mice were inoculated i.v. with 1.0 x 104 viable conidia or saline and challenged i.v. with 1.0 x 106 conidia after 7, 15, or 21 days. No protection against challenge was found after 7 days. However, significant and reproducible protection was observed after 15 and 21 days. Mortality was reduced from 90 % in control mice to 53 % in preinfected mice 40 days after challenge (P = 0.0002). Increased survival was correlated with decreased content of chitin in lungs, liver, and kidneys 4 and 7 days after challenge (P < 0.05). Mice were again inoculated with 1.0 x 104 conidia or saline, and after 21 days, 1.0 x 10 ' or 2.0 x 108 splenocytes were transferred to naive syngeneic recipients; 2.0 x 10 ' immune splenocytes conferred significant protection (P = 0.0001) against i.v. challenge with 1.0 x 106 conidia, and mortality decreased from 83 to 48 % 40 days after challenge. Transfer of immune serum offered no protection despite the presence of antibody against a hyphal homogenate ofA.fmigatus, which was absent in the sera o