CONTRIBUTION OF INTERFERON-GAMMA IN PROTECTING MICE DURING PULMONARY AND DISSEMINATED INFECTION WITH CRYPTOCOCCUS-NEOFORMANS

In the present study, the role of interferon-gamma (IFN-gamma) in the host resistance against Cryptococcus neoformans was examined using a m urine model of pulmonary and disseminated infection. In this model, mi ce were infected intratracheally with live yeast cells, and the histol ogical changes in the lungs and the number of microorganisms in the lu ng and brain were compared in mice treated and untreated with anti-IFN -gamma monoclonal antibody (mAb) to define the contribution of endogen ously synthesized IFN-gamma in the natural course of infection. Admini stration of this mAb reduced the accumulation of inflammatory cells in the alveolar septa, peribronchial and perivascular areas, and promote d the expansive growth of microorganisms in the alveoli and destructio n of alveolar structure. The neutralization of endogenous IFN-gamma by mAb increased the number of microorganisms in the lung and brain, and significantly shortened the survival time of infected mice. On the ot her hand, administration of IFN-gamma decreased the number of microorg anisms in these organs, and significantly extended their survival time . Considered together, our results suggest that endogenous IFN-gamma p rotects mice from infection with C. neoformans by inducing a cellular inflammatory response, potentiating the clearance of microorganism fro m the lungs and preventing its dissemination into the central nervous system.