Differences between Trypanosoma brucei gambiense groups 1 and 2 in their resistance to killing by trypanolytic factor 1

PLoS Negl Trop Dis. 2011 Sep;5(9):e1287. doi: 10.1371/journal.pntd.0001287. Epub 2011 Sep 6.

Abstract

Background: The three sub-species of Trypanosoma brucei are important pathogens of sub-Saharan Africa. T. b. brucei is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. T. b. rhodesiense and T. b. gambiense are able to resist lysis by TLF. There are two distinct sub-groups of T. b. gambiense that differ genetically and by human serum resistance phenotypes. Group 1 T. b. gambiense have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 T. b. gambiense are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (HpHbR)) gene. Here we investigate if this is also true in group 2 parasites.

Methodology: Isogenic resistant and sensitive group 2 T. b. gambiense were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the HpHbR gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to T. b. brucei. Both resistant and sensitive group 2, as well as group 1 T. b. gambiense, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.

Conclusions: Our data indicate that, despite group 1 T. b. gambiense avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 T. b. gambiense is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 T. b. gambiense variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of HpHbR. Thus there are differences in the mechanism of human serum resistance between T. b. gambiense groups 1 and 2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein L1
  • Apolipoproteins / immunology
  • Apolipoproteins / pharmacology*
  • Biological Products / pharmacology*
  • Cell Survival / drug effects
  • Drug Resistance
  • Humans
  • Lipoproteins, HDL / immunology
  • Lipoproteins, HDL / pharmacology*
  • Parasitic Sensitivity Tests
  • Serum / immunology
  • Serum / parasitology
  • Trypanosoma brucei gambiense / classification
  • Trypanosoma brucei gambiense / drug effects*
  • Trypanosoma brucei gambiense / immunology
  • Trypanosoma brucei gambiense / physiology

Substances

  • APOL1 protein, human
  • Apolipoprotein L1
  • Apolipoproteins
  • Biological Products
  • Lipoproteins, HDL
  • TLF1 protein, human