Inducible Natural IgMs Bridge Trypanosome Lytic Factor Assembly and Parasite Recognition

2019 ◽  
Author(s):  
Joseph Verdi ◽  
Ronnie Zipkin ◽  
Elani Hillman ◽  
Rahel A. Gertsch ◽  
Sarah J. Pangburn ◽  
...  
Keyword(s):  
Trypanosome Lytic Factor

scholarly journals Activity of trypanosome lytic factor: a novel component of innate immunity

2009 ◽  
Vol 4 (7) ◽  
pp. 789-796 ◽  
Author(s):  
Russell Thomson ◽  
Marie Samanovic ◽  
Jayne Raper
Keyword(s):  
Innate Immunity ◽  
Trypanosome Lytic Factor

scholarly journals A co-evolutionary arms race: trypanosomes shaping the human genome, humans shaping the trypanosome genome

Parasitology ◽  
2014 ◽  
Vol 142 (S1) ◽  
pp. S108-S119 ◽  
Author(s):  
PAUL CAPEWELL ◽  
ANNELI COOPER ◽  
CAROLINE CLUCAS ◽  
WILLIAM WEIR ◽  
ANNETTE MACLEOD
Keyword(s):  
Trypanosoma Brucei ◽  
Protein Complexes ◽  
Resistance Mechanism ◽  
Surface Glycoprotein ◽  
Trypanosoma Brucei Rhodesiense ◽  
Counter Measures ◽  
Multiple Components ◽  
Variable Surface ◽  
Trypanosome Lytic Factor ◽  
Resistance To Infection

SUMMARYTrypanosoma brucei is the causative agent of African sleeping sickness in humans and one of several pathogens that cause the related veterinary disease Nagana. A complex co-evolution has occurred between these parasites and primates that led to the emergence of trypanosome-specific defences and counter-measures. The first line of defence in humans and several other catarrhine primates is the trypanolytic protein apolipoprotein-L1 (APOL1) found within two serum protein complexes, trypanosome lytic factor 1 and 2 (TLF-1 and TLF-2). Two sub-species of T. brucei have evolved specific mechanisms to overcome this innate resistance, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. In T. b. rhodesiense, the presence of the serum resistance associated (SRA) gene, a truncated variable surface glycoprotein (VSG), is sufficient to confer resistance to lysis. The resistance mechanism of T. b. gambiense is more complex, involving multiple components: reduction in binding affinity of a receptor for TLF, increased cysteine protease activity and the presence of the truncated VSG, T. b. gambiense-specific glycoprotein (TgsGP). In a striking example of co-evolution, evidence is emerging that primates are responding to challenge by T. b. gambiense and T. b. rhodesiense, with several populations of humans and primates displaying resistance to infection by these two sub-species.

scholarly journals Serum Resistance-Associated Protein Blocks Lysosomal Targeting of Trypanosome Lytic Factor in Trypanosoma brucei

2006 ◽  
Vol 5 (1) ◽  
pp. 132-139 ◽  
Author(s):  
Monika W. Oli ◽  
Laura F. Cotlin ◽  
April M. Shiflett ◽  
Stephen L. Hajduk
Keyword(s):  
Trypanosoma Brucei ◽  
Density Lipoprotein ◽  
Trypanosoma Brucei Rhodesiense ◽  
Apolipoprotein A ◽  
Cytoplasmic Vesicles ◽  
Wide Range ◽  
Trypanosome Lytic Factor ◽  
Normal Human ◽  
Human High Density Lipoprotein ◽  
A Minor

ABSTRACT Trypanosoma brucei brucei is the causative agent of nagana in cattle and can infect a wide range of mammals but is unable to infect humans because it is susceptible to the innate cytotoxic activity of normal human serum. A minor subfraction of human high-density lipoprotein (HDL) containing apolipoprotein A-I (apoA-I), apolipoprotein L-I (apoL-I), and haptoglobin-related protein (Hpr) provides this innate protection against T. b. brucei infection. This HDL subfraction, called trypanosome lytic factor (TLF), kills T. b. brucei following receptor binding, endocytosis, and lysosomal localization. Trypanosoma brucei rhodesiense, which is morphologically and physiologically indistinguishable from T. b. brucei, is resistant to TLF-mediated killing and causes human African sleeping sickness. Human infectivity by T. b. rhodesiense correlates with the evolution of a resistance-associated protein (SRA) that is able to ablate TLF killing. To examine the mechanism of TLF resistance, we transfected T. b. brucei with an epitope-tagged SRA gene. Transfected T. b. brucei expressed SRA mRNA at levels comparable to those in T. b. rhodesiense and was highly resistant to TLF. In the SRA-transfected cells, intracellular trafficking of TLF was altered, with TLF being mainly localized to a subset of SRA-containing cytoplasmic vesicles but not to the lysosome. These results indicate that the cellular distribution of TLF is influenced by SRA expression and may directly determine the organism's susceptibility to TLF.

scholarly journals Hydrodynamic gene delivery of baboon trypanosome lytic factor eliminates both animal and human-infective African trypanosomes

2009 ◽  
Vol 106 (46) ◽  
pp. 19509-19514 ◽  
Author(s):  
R. Thomson ◽  
P. Molina-Portela ◽  
H. Mott ◽  
M. Carrington ◽  
J. Raper
Keyword(s):  
Gene Delivery ◽  
African Trypanosomes ◽  
Trypanosome Lytic Factor

scholarly journals Characterization of a Novel Trypanosome Lytic Factor from Human Serum

1999 ◽  
Vol 67 (4) ◽  
pp. 1910-1916 ◽  
Author(s):  
Jayne Raper ◽  
Ramie Fung ◽  
Jorge Ghiso ◽  
Victor Nussenzweig ◽  
Stephen Tomlinson
Keyword(s):  
Human Serum ◽  
Specific Activity ◽  
Immunoglobulin M ◽  
Natural Resistance ◽  
Related Protein ◽  
Trypanosoma Brucei Brucei ◽  
Apolipoprotein A ◽  
Trypanosome Lytic Factor ◽  
Normal Human

ABSTRACT Natural resistance of humans to the cattle pathogenTrypanosoma brucei brucei has been attributed to the presence in human serum of nonimmune factors that lyse the parasite. Normal human serum contains two trypanosome lytic factors (TLFs). TLF1 is a 500-kDa lipoprotein, which is reported to contain apolipoprotein A-I (apoA-I), haptoglobin-related protein (Hpr), hemoglobin, paraoxonase, and apoA-II, whereas TLF2 is a larger, poorly characterized particle. We report here a new immunoaffinity-based purification procedure for TLF2 and TLF1, as well as further characterization of the components of each purified TLF. Immunoaffinity-purified TLF1 has a specific activity 10-fold higher than that of TLF1 purified by previously described methods. Moreover, we find that TLF1 is a lipoprotein particle that contains mainly apoA-I and Hpr, trace amounts of paraoxonase, apoA-II, and haptoglobin, but no detectable hemoglobin. Characterization of TLF2 reveals that it is a 1,000-kDa protein complex containing mainly immunoglobulin M, apoA-I, and Hpr but less than 1% detectable lipid.

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