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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.

Differences between Trypanosoma brucei gambiense Groups 1 and 2 in Their Resistance to Killing by Trypanolytic Factor 1