Experimental disseminated aspergillosis in mice: Histopathological study

Objective. - Systemic response to intravenous administration of Aspergillus fumigatus conidia was investigated in laboratory mice by survival/mortality, peripheral blood Leukocyte response and histopathological evaluation of Lung, liver, kidney and spleen. Methods. - Female C57Bl/6 mice were inoculated intravenously with 10(6) -5 x 10(7) conidia of A. fumigatus (human isolate). Survival was monitored for two weeks. Histopathological analysis of organ was conducted postmortem and in survivors. Peripheral blood cells and leukocyte aggregation were determined in survivors. Results. - Administration of all doses of A. fumigatus conidia caused mortality, but the highest mortality rate and the shortest time of survival were noted at the highest doses applied. Increased peripheral blood lymphocyte counts and their propensity to aggregate were observed in survivors. Histological analysis revealed : (1) pulmonary inflammatory response proportional to the applied dose of conidia with detectable fungi in lungs of animals that received the highest applied dose; (2) pronounced kidney inflammatory response with variable intensity of tubular dilation in survivors versus tubular destruction in nonsurvivors and proteinuria as well as hemoglobinuria at the highest doses applied; (3) presence of microabscesses in the liver; (4) white pulp hyperplasia and dose-dependent increase in lymphoid follicles in the spleen of infected animals that survived. Conclusion. - Lymphocytosis and state of aggregation/adhesion in survivors and local histotogically evident inflammatory response in all examined organs of mice characterize the response to systemic application of A. fumigatus conidia. The results obtained may contribute to our understanding of pathological mechanisms underlying disseminated aspergillosis and to the evaluation of therapeutic interventions that might improve survival or Lessen pathology. (C) 2008 Published by Elsevier Masson SAS.nul