title: Secreted virulence factors and immune evasion in visceral leishmaniasis.
abstract: Evasion or subversion of host immune responses is a well-established paradigm in infection with visceralizing leishmania. In this review, we summarize current findings supporting a model in which leishmania target host regulatory molecules and pathways, such as the PTP SHP-1 and the PI3K/Akt signaling cascade, to prevent effective macrophage activation. Furthermore, we describe how virulence factors, secreted by leishmania, interfere with macrophage intracellular signaling. Finally, we discuss mechanisms of secretion and provide evidence that leishmania use a remarkably adept, exosome-based secretion mechanism to export and deliver effector molecules to host cells. In addition to representing a novel mechanism for trafficking of virulence factors across membranes, recent findings indicate that leishmania exosomes may have potential as vaccine candidates.
authors.affiliation: Department of Medicine Division of Infectious Diseases and the Experimental Medicine Program, University of British Columbia, Vancouver, Canada.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lambertz
authors.forename: Judith Maxwell
authors.initials: JM
authors.lastname: Silverman
authors.forename: Devki
authors.initials: D
authors.lastname: Nandan
authors.forename: W Robert
authors.initials: WR
authors.lastname: McMaster
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Foster
authors.forename: Neil E
authors.initials: NE
authors.lastname: Reiner
mesh_terms: D000818:Animals; D006801:Humans; D007893:Leishmania donovani / Q000276:immunology* / Q000378:metabolism; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism; D021381:Protein Transport / Q000276:immunology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000276:immunology / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D015800:Protozoan Proteins / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D037521:Virulence Factors / Q000276:immunology* / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D037521:Virulence Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6