Divergent patterns of pulmonary blastomycosis induced by conidia and yeasts in athymic and euthymic mice

Abstract

Athymic nude (nu/nu) mice are uniformly more susceptible than euthymic nu/+ mice to lethal infection with intranasally inoculated Blastomyces dermatitidis, whether infection is initiated by yeasts or conidia. Conidial infection requires a high inoculum size; the disease produced is prolonged and disseminated. Yeasts are infective at a low inoculum size and produce a rapidly fatal pneumonia. Thymus transplantation is more protective for conidia-infected than yeast-infected nude mice, presumably because the disease course is long enough for an effect to become demonstrable. Yeast inocula multiply more rapidly in the lungs than do conidial inocula. This may relate to the greater susceptibility of conidia to heterophils evoked in the airways, and the fact that yeasts derived from conidial inocula must survive in the face of an established inflammatory reaction. When yeasts and conidia are inoculated simultaneously, the disease produced is less severe than when yeasts are inoculated alone, presumably because of a more intense and diffuse inflammatory response engendered by the conidia. Suppression of conidia-derived yeast replication is demonstrable for at least 1 wk in nu/nu mice and for 2 to 3 wk in nu/+ mice. The latter delay appears attributable to the intact immune system in nu/+ mice, and the probability that cellular immunity limits the subsequent replication of yeasts. Eventually, the immune response fails to control yeast replication, and the mice succumb. These studies provide further insights into the role of the thymus in host defense against B. dermatitidis and the basis for the differential pace of infection when mice are infected with yeasts or conidia.