Paracoccidioides Spp.: Virulence Factors and Immune-Evasion Strategies

Figure 2

Diagram of proposed Paracoccidioides spp. immune-evasion mechanisms. (a) Shielding of stimulatory PAMPs. The cell wall beta-glucan present in the fungus saprophytic forms (conidia and mycelia) is recognized by the macrophage Dectin-1 receptor; however, pathogenic yeast cell α-(1,3)-glucan masks β-(1,3)-glucan, avoiding its recognition. (b) Intracellular survival. Paracoccidiodes spp. use several strategies to overcome the host harsh environment, among them are the following: (1) promoting invasion to the pulmonary epithelial cells by altering their cytoskeleton structure, a process assisted by gp43; (2) avoiding phagocytosis by displaying an enlarged multibudding morphology, boosted by Cdc42 expression, which physically impairs engulfment by macrophages; and (3) adapting to the host environment. The phagocytosed fungus shifts its metabolism to tolerate macrophage stress conditions and even modulate host apoptosis enabling fungal killing. (c) Altering T-cell repertoire. During acute fungal infections, yeast cells invade the thymus altering its epithelial cells’ spatial arrangement crucial for T-cell differentiation and pathogen-specific immune response.

(a) Shielding of stimulatory PAMPs

(b) Intracellular survival

(c) Altering T-cell repertoire