title: Phosphatidylserine exposure on the surface of Leishmania amazonensis amastigotes modulates in vivo infection and dendritic cell function.
abstract: Leishmania amazonensis parasites can cause diverse forms of leishmaniasis in humans and persistent lesions in most inbred strains of mice. In both cases, the infection is characterized by a marked immunosuppression of the host. We previously showed that amastigote forms of the parasite make use of surface-exposed phosphatidylserine (PS) molecules to infect host cells and promote alternative macrophage activation, leading to uncontrolled intracellular proliferation of the parasites. In this study, we demonstrated that treatment of infected mice with a PS-targeting monoclonal antibody ameliorated parasite loads and lesion development, which correlated with increased proliferative responses by lymphocytes. In addition, we observed an enhanced dendritic cell (DC) activation and antigen presentation in vitro. Our data imply that the recognition of PS exposed on the surface of amastigotes plays a role in down-modulating DC functions, in a matter similar to that of apoptotic cell clearance. This study provides new information regarding the mechanism of immune suppression in Leishmania infection.
authors.affiliation: Morphological Sciences Program, Biomedical Sciences Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.|Campus UFRJ Macaé, Pólo Universitário, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.|Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: J L M
authors.initials: JLM
authors.lastname: Wanderley
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Thorpe
authors.affiliation: Parasitology Department, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo, Brazil.|Laboratory of Cellular Biology, Institute Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Barcinski
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.|Department of Pathology, Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Soong
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology*; D004195:Disease Models, Animal; D005260:Female; D057131:Immune Evasion; D007108:Immune Tolerance; D007894:Leishmania mexicana / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D010718:Phosphatidylserines / Q000032:analysis / Q000276:immunology*
chemical_list: D010718:Phosphatidylserines