Complement-Mediated Differential Immune Response of Human Macrophages to Species Through Interaction With Their Cell Wall Peptidorhamnomannans.

In this study, the human immune response mechanisms against and , two causative agents of human and animal sporotrichosis, were investigated. The interaction of and with human monocyte-derived macrophages (hMDMs) was shown to be dependent on the thermolabile serum complement protein C3, which facilitated the phagocytosis of yeast cells through opsonization. The peptidorhamnomannan (PRM) component of the cell walls of these two yeasts was found to be one of their surfaces exposed pathogen-associated molecular pattern (PAMP), leading to activation of the complement system and deposition of C3b on the yeast surfaces. PRM also showed direct interaction with CD11b, the specific component of the complement receptor-3 (CR3). Furthermore, the blockade of CR3 specifically impacted the interleukin (IL)-1β secretion by hMDM in response to both and , suggesting that the host complement system plays an essential role in the inflammatory immune response against these species. Nevertheless, the structural differences in the PRMs of the two species, as revealed by NMR, were related to the differences observed in the host complement activation pathways. Together, this work reports a new PAMP of the cell surface of pathogenic fungi playing a role through the activation of complement system and CR3 receptor mediating an inflammatory response to species.