GP43 from Paracoccidioides brasiliensis inhibits macrophage functions. An evasion mechanism of the fungus.
Macrophages constitute one of the primary cellular mechanisms that impairs parasite invasion of host tissues. The phagocytic and microbicidal properties of these cells can be modulated by specific membrane receptors involved in cell-microorganism interactions. Gp43, the main antigen secreted by Paracoccidiodes brasiliensis (Pb), the causative agent of Paracoccidioidomycosis, is a high mannose glycoprotein. The role played by gp43 in the pathogenesis of the disease is not completely known. Here, we describe the influence of this molecule on the interaction between peritoneal murine macrophages and Pb. Phagocytosis of Pb, live or heat-killed, by adherent peritoneal cells from both, B10.A (susceptible) and A/Sn (resistant) mice, was evaluated. Addition of different concentrations of gp43 to the culture medium inhibited, in a dose-dependent pattern, phagocytosis of live or heat-killed Pb by peritoneal macrophages from both B10.A and A/Sn mice. Gp43 also inhibits phagocytosis of zymosan particles but did not interfere with the uptake of opsonized sheep red blood cells. It was also shown that both gp43 and heat-killed Pb have an inhibitory effect on the release of NO by zymosan stimulated macrophages. Finally, we demonstrated that gp43 inhibits the fungicidal ability of macrophages from both lineages. Based on these data, it is suggested that gp43 can be considered one of the evasion mechanisms for the installation of primary infection in susceptible hosts.
Flavia Popi
Ana Flavia
AF
Discipline of Immunology, Department of Microbiology, Immunology, and Parasitology, Federal University of São Paulo, São Paulo, Brazil.
Lopes
José Daniel
JD
Mariano
Mario
M
D000818:Animals; D000946:Antigens, Fungal / Q000502:physiology*; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D017077:Culture Media, Conditioned; D005656:Fungal Proteins / Q000494:pharmacology / Q000502:physiology*; D006023:Glycoproteins / Q000494:pharmacology / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009569:Nitric Oxide / Q000378:metabolism; D009844:Oligosaccharides / Q000494:pharmacology / Q000502:physiology*; D010228:Paracoccidioides / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects
C103180:43 kDa protein, Paracoccidioides; D000946:Antigens, Fungal; D017077:Culture Media, Conditioned; D005656:Fungal Proteins; D006023:Glycoproteins; D009844:Oligosaccharides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide