| Disease Introduction Mechanism | Histoplasmosis, caused by Histoplasma capsulatum (HC) is the most prevalent fungal respiratory disease in the US, affecting 500,000 individuals each year. Infection typically results in a mild, often asymptomatic respiratory illness but may progress to life-threatening systemic disease, particularly in immunocompromised individuals. Upon inhalation, Hc is ingested by resident pulmonary macrophages, where the fungus replicates and subsequently disseminates to other organs. Macrophages are considered the most important effector cells in host resistance against histoplasmosis by functioning in both innate and cell-mediated im- munity. However, resolution of histoplasmosis depends on the activation of cell-mediated immunity, in particular effective T cell responses (1). Both CD4 and CD8 T cells contribute to host resistance in primary Hc infection. Reduction of CD4 T cells results in fatal histoplasmosis in naı ¨ve mice and adoptive transfer of Hc reactive CD4 T cells confers protection. In mice that lack CD8 T cells, clearance of Hc from organs is impaired. Sublethal infection with Hc evokes a Th1-like response in mice, characterized by the dominance of IL-12, TNF- , and IFN- during the acute phase of infection. Upon induction of cell-mediated immunity and the production of cytokines, macrophages are activated, and the fungus is eliminated. The importance of B cells in primary histoplasmosis is less critical, however, in B cell- deficient animals the progression toward lethal infection is accelerated in reactivation disease. |
