Biological Variation Among African Trypanosomes: I. Clonal Expression of Virulence Is Not Linked to the Variant Surface Glycoprotein or the Variant Surface Glycoprotein Gene Telomeric Expression Site

Modulation of innate immunity by African Trypanosomes

“…While scavenger receptors were once thought to serve simply as nonopsonic phagocytic receptors for many ligands, it is now clear that there are direct signaling events generated by ligand engagement of these receptors, including SR-A [as shown in our earlier parasiteunrelated studies; ) and by others ( PAMP recognition by combinatorial activation of multiple PRRs appears to be an evolutionarily conserved but poorly understood and complex phenomenon (Amit et al 2009). To date it is clear that TLR-independent signaling is triggered by GIP-sVSG binding to SR-A, and that NFkB and MAPK signaling pathways are activated after internalization (Leppert et al 2007;Freeman, Mansfield and Paulnock, unpublished observations;Mansfield and Paulnock, 2010). This GIP-sVSG-SR-A ligand/ receptor interaction activates subsequent TLRdependent signaling events that then down-regulate the initial response (Leppert et al 2007;Mansfield and Paulnock, unpublished observations).…”

“…Activation of MPs and DCs is dependent upon SR-A mediated, clathrin-dependent internalization of GIP-sVSG and delivery to late endolysosomal compartments. Aadapted from Leppert et al (2007) and Mansfield and Paulnock (2010).…”

“…GIP-sVSG-induced NFkB signaling is enhanced in the absence of TLR signaling (A): irreversible Traf6 inhibitor;(Leppert et al 2007) and TLR9 inhibitory ODN (B): TLR9 iODN 2088;(Mansfield and Paulnock, 2010).…”

Prospects for vaccination against pathogenic African trypanosomes

“…A number of variant antigenic types (VATs) from T. b. rhodesiense LouTat 1‐infected mice at early, intermediate and late time points of infection, as well as sublines and subclones of trypanosomes from longer‐term passage of LouTat 1 through mice, were assessed for their virulence characteristics, and one representative trypanosome population, designated T. b. rhodesiense subclone LouTat 1A, was selected from a terminal time point of infection for further analysis . LouTat 1A displayed a single uncontrolled peak of parasitemia and caused death in a genetically “resistant” mouse strain (and in all other relatively resistant or susceptible strains of mice) in approximately 3‐4 days post‐infection; in contrast, the “parental” clone LouTat 1 gave rise to multiple peaks of parasitemia and a prolonged survival time of over 60 days in the same resistant mouse strain .…”

“…Importantly, relative virulence in the LouTat serodeme was not a mouse‐specific phenomenon, as other host animal species including domestic animals and nonhuman primates were also affected . Importantly T. b. rhodesiense LouTat 1 and LouTat 1A were shown to express the same VSG gene and surface coat, and to utilize the same telomeric VSG gene expression site (ES) . Thus, differences in virulence were not associated with the VSG or with the active VSG ES.…”