Intercellular communication between parasites and with host cells provides mechanisms for parasite development, immune evasion and disease pathology. Bloodstream African trypanosomes produce membranous nanotubes that originate from the flagellar membrane and disassociate into free extracellular vesicles (EVs). Trypanosome EVs contain several flagellar proteins that contribute to virulence and Trypanosoma brucei rhodesiense EVs contain the serum resistance-associated protein (SRA) necessary for human infectivity. T. b. rhodesiense EVs transfer SRA to non-human infectious trypanosomes allowing evasion of human innate immunity. Trypanosome EVs can also fuse with mammalian erythrocytes resulting in rapid erythrocyte clearance and anemia. These data indicate that trypanosome EVs are organelles mediating non-hereditary virulence factor transfer and causing host erythrocyte remodeling inducing anemia.

The aim of this study was to identify multicomponent complexes involved in kinetoplastid mitochondrial mRNA editing. Mitochondrial extracts from Trypanosoma brucei were fractionated on 10–30% glycerol gradients and assayed for RNAs and activities potentially involved in editing, including pre‐edited mRNA, guide RNA (gRNA), endonuclease, terminal uridylyltransferase (TUTase), RNA ligase and gRNA‐mRNA chimera‐forming activities. These experiments suggest that two distinct editing complexes exist. Complex I (19S) consists of gRNA, TUTase, RNA ligase and chimera‐forming activity. Complex II (35–40S) is composed of gRNA, preedited mRNA, RNA ligase and chimera‐forming activity. These studies provide the first evidence that editing occurs in a multicomponent complex. The possible roles of complex I, complex II and RNA ligase in editing are discussed.

Human innate immunity to non-pathogenic species of African trypanosomes is provided by human high density lipoprotein (HDL) particles. Here we show that native human HDLs containing haptoglobin-related protein (Hpr), apolipoprotein L-I (apoL-I) and apolipoprotein A-I (apoA-I) are the principle antimicrobial molecules providing protection from trypanosome infection. Other HDL subclasses containing either apoA-I and apoL-I or apoA-I and Hpr have reduced trypanolytic activity, whereas HDL subclasses lacking apoL-I and Hpr are non-toxic to trypanosomes. Highly purified, lipid-free Hpr and apoL-I were both toxic to Trypanosoma brucei brucei but with specific activities at least 500-fold less than those of native HDLs, suggesting that association of these apolipoproteins within the HDL particle was necessary for optimal cytotoxicity. These studies show that HDLs can serve as platforms for the assembly of multiple synergistic proteins and that these assemblies may play a critical role in the evolution of primate-specific innate immunity to trypanosome infection. High density lipoprotein (HDL)2 has several well established physiological activities. The best understood of these is the ability of HDL to protect against atherosclerotic cardiovascular disease by promoting the efflux of excess cholesterol from peripheral tissues and its subsequent transport to the liver for excretion. In addition, apolipoproteins and enzymes carried by HDL have antioxidant activities that inhibit the oxidative modification of low density lipoprotein (LDL), thereby reducing the atherogenicity of these lipoproteins. A less well known activity of HDL is an antimicrobial property that protects some primates from infection by certain eukaryotic pathogens. In these primate species, HDL apolipoproteins have been proposed to have novel innate immune protective functions that provide selective protection against infection.One such innate immune activity in the serum of humans, apes, and old world monkeys limits the host range of Trypanosoma brucei brucei to non-primate mammals (1). This activity fractionates with a minor subclass of human HDL termed trypanosome lytic factor 1 (TLF-1) that, like all HDLs, is composed of apolipoproteins, phospholipids, and neutral lipids (2, 3). Trypanosome killing by these cytotoxic HDLs requires high affinity binding to receptors on the trypanosome surface, endocytosis, and lysosomal localization (4 -8). Following lysosomal acidification, destabilization of the lysosome membrane is facilitated by either free radical-mediated lipid peroxidation or pore formation (9 -11). Two HDL-associated proteins have been implicated in the toxicity of TLF-1, haptoglobin-related protein (Hpr) and apolipoprotein L-I (apoL-I) (12, 13).Haptoglobin-related protein differs by only 27 amino acids from human haptoglobin, an acute phase serum protein that binds hemoglobin released from red blood cells during trauma or infection and transfers the hemoglobin to liver cells for detoxification (14,15). However, Hpr does not bind hemoglobin, and...

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Trypanosoma brucei spp. cause African human and animal trypanosomiasis, a burden on health and economy in Africa. These hemoflagellates are distinguished by a kinetoplast nucleoid containing mitochondrial DNAs of two kinds: maxicircles encoding ribosomal RNAs (rRNAs) and proteins and minicircles bearing guide RNAs (gRNAs) for mRNA editing. All RNAs are produced