Immunohistopathology of murine pulmonary histoplasmosis during normal and hypersensitive conditions

Pulmonary histoplasmosis was induced in nonimmunized and immunized Balb-C nu/+ mice. The lung tissue burden of H. capsulatum, histopathology, the size of the inflammatory area, and the numbers of total T lymphocytes and subtypes in situ were evaluated serially after challenge. Over 3 days previously immunized mice developed a large lymphocyte/macrophage inflammatory response. This rapidly decreased in the next 2 wk. In contrast, the nonimmunized control mice developed a predominantly polymorphonuclear infiltrate that evolved more slowly over the first week of infection. This initial response was nonspecific but, after the first week, shifted to lymphocytes and granuloma formation. The lymphocyte infiltration in both immunized and nonimmunized mice was predominantly CD4. Previously immunized mice had a rapid decrease in tissue counts of H. capsulatum after Day 3, but nonimmunized mice continued to have increased counts through Day 7 after infection. These studies reproduce in the mouse model a host response similar to acute reinfection histoplasmosis in the human. In this condition an intense cell-mediated inflammatory response is thought to be elicited by fungal antigens and to represent host reaction rather than fungal replication. Our experimental model added new information relevant to the understanding of the pathogenesis of this process.