The Trojan Horse Model in Paracoccidioides: A Fantastic Pathway to Survive Infecting Human Cells

Abstract

Paracoccidioidomycosis (PCM) is the most relevant systemic endemic mycosis limited to Latin American countries. The etiological agents are thermally dimorphic species of the genus Paracoccidioides. Infection occurs via respiratory tract by inhalation of propagules from the environmental (saprophytic) phase. In the lung alveoli the fungus converts to the characteristic yeast phase (parasitic) where interact with extracellular matrix proteins, epithelial cells, and the host cellular immunity. The response involves phagocytic cells recognition but intracellular Paracoccidioides have demonstrated the ability to survive and also multiply inside the neutrophils, macrophages, giant cells, and dendritic cells. Persistence of Paracoccidioides as facultative intracellular pathogen is important in terms of the fungal load but also regarding to the possibility to disseminate penetrating other tissues even protected by the phagocytes. This strategy to invade other organs via transmigration of infected phagocytes is called Trojan horse mechanism and it was also described for other fungi and considered a factor of pathogenicity. This mini review comprises a literature revision of the spectrum of tools and mechanisms displayed by Paracoccidioides to overcame phagocytosis, discusses the Trojan horse model and the immunological context in proven models or the possibility that Paracoccidioides apply this tool for dissemination to other tissues.

Keywords: Paracoccidioidomycosis; dissemination; immune response evasion; internalized parasitic cells; transmigration.

Figure 1

Cellular response to Paracoccidioides infection in the lung and immune-evasion mechanisms. Upon inhalation the saprophytic form converts to the yeast-like parasitic and trigger the host cellular immune response. Phagocytes are motivated to clear the invasive fungi. In addition to its own structural virulence determinants such as gp43, melanin, among others, Paracoccidioides spp. applies several strategies to overcome the host harsh environment, including: modulate host apoptosis, metabolic adaptations, and expression of genes to achieve an inanition mode and also resistance to the host oxidative burst. When intracellular survival is possible, part of the phagocytosed fungi could be transported by DCs/macrophages to lymphoid tissues or other organs via circulation as facultative intracellular pathogens but protected by phagocytes (Trojan horse mechanism).