Detection of histoplasmal antigens in mice undergoing experimental pulmonary histoplasmosis

A micro-ELISA assay was developed for the quantitation of Histoplasma capsulatum antigen in lungs, bronchoalveolar lavage fluid (BALF), and serum of intranasally infected mice. As little as 0.2 ng of antigen/ml could be detected. During the course of experimental histoplasmosis, immunologically intact, thymus-containing mice (nu/+) had detectable histoplasmal antigens in their lungs, serum, and BALF within 1 day of challenge. Lung, BALF, and serum antigen concentration rose to a peak 2 wk after challenge; in nu/+ mice, antigen concentration then declined through the next 2 wk. In contrast, athymic nude mice have depressed cell-mediated immunity; their antigen concentration continued to rise throughout the course of progressive, ultimately lethal, illness. Antigen concentrations correlated with quantitative cultures of the lungs and BALF. There was little cross reactivity in mice challenged intranasally with Candida albicans or Blastomyces dermatitidis. The sensitivity of this test, and the apparently minimal cross reactivity, suggest that the micro-ELISA for histoplasmal antigen might have significant clinical application in diagnosing and monitoring the course of histoplasmosis.