Figure 2.

Pathogenesis of histoplasmosis. Aerosolized microconidia are inhaled by the host. Host temperature (37 °C) triggers morphological transformation to yeast. Surfactant A and D (collectins) display a direct fungicidal role through a calcium-dependent mechanism of yeast permeabilization. Heat shock protein 60 (HSP60) is recognized by complement receptor 3 (CR3) and promotes phagocytosis. If Dectin-1 is activated by interaction with 1-3 β D glucan, the macrophage is able to produce a profound inflammatory cascade. To avoid it, the yeast covers the 1-3 β D glucan with 1-3 α glucan. Once in the phagolysosome, antigen M inhibits the reactive oxygen species (ROS). The infected macrophage can migrate to any other organ in the body, including liver, spleen, and bone marrow. Dendritic cells are able to kill the yeast and present antigens to T helper cells (Th0) and promote their polarization into Th1, which in turn increases pro-inflammatory cytokines leading to further macrophage activation.