Experimental pulmonary histoplasmosis and emphysema

Chronic pulmonary histoplasmosis often occurs in the setting of emphysema. However, it is unknown whether emphysema directly predisposes to the development of the necrotizing lesions of chronic pulmonary histoplasmosis. We evaluated this possibility using a murine model of pulmonary histoplasmosis. Using intratracheal inoculation of elastase, we induced pulmonary emphysema in Balb/c mice. When mice with emphysema were challenged intranasally with H. capsulatum (HC) yeast cells, the course of their disease was not significantly different from that of normal mice. Mice were also exposed to HC antigens by sublethal intranasal challenge with viable or heat-killed HC, or immunized with histoplasmin. Prior sublethal challenge with viable HC did not cause prolonged illness or increased mortality in the setting of emphysema. In contrast, such mice were protected against a severe rechallenge. Additional studies showed that intranasal administration of heat-killed HC or subcutaneous immunization with histoplasmal antigens had neither protective nor deleterious effects on the course of histoplasmosis. Therefore, in this murine model, we could not substantiate an interaction of underlying emphysema with acute primary or rechallenge pulmonary histoplasmosis.